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Extemporaneous oral liquid preparations are commonly used when there is no commercially available dosage form for adjustable dosing. In most cases, there is a lack of stability data to allow for an accurately assigned shelf life and storage conditions to give greater confidence of product safety and efficacy over its shelf life. The aim of this study was to evaluate the physical, chemical and microbiological stability of an extemporaneous oral liquid suspension of losartan potassium, 5 mg/mL, used to treat paediatric hypertension in Our Lady's Children's Hospital Crumlin, Ireland. The losartan content of extemporaneous oral suspensions, prepared with and without addition of water, was measured by UV and confirmed by HPLC analysis. Suspensions were stored at 4 °C and room temperature (RT) and were monitored for changes in; pH, colour, odour, re-dispersibility, Total Aerobic Microbial Count, Total Yeast and Mould Count and absence of E. coli. Results showed that suspensions prepared by both methods, stored at 4 °C and RT, were physically and microbiologically stable over 28 days. Initial losartan content of all suspensions was lower than expected at 80-81% and did not change significantly over the 28 days. HPLC and NMR did not detect degradation of losartan in the samples. Suspensions prepared in water showed 100% losartan content. The reduced initial losartan content was confirmed by HPLC and was related to the acidic pH of the suspension vehicle. Physiochemical properties of the drug are important factors for consideration in the selection of suspension vehicle for extemporaneous compounding of oral suspensions as they can influence the quality, homogeneity and efficacy of these preparations.
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Antihipertensivos/administración & dosificación , Antihipertensivos/química , Bacterias/efectos de los fármacos , Losartán/administración & dosificación , Losartán/química , Comprimidos/química , Administración Oral , Composición de Medicamentos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , SuspensionesRESUMEN
Within this work, we describe the design and synthesis of a range of novel thiochromanones based on natural products reported to possess anti-leishmanial action, and their synthetic derivatives. All compounds were elaborated via the key intermediate 2,2,6-trimethoxythiochromanone, which was modified at the benzylic position to afford various ester, amine and amide analogues, substituted by chains of varying lipophilicity. Upon testing in Leishmania, IC50 values revealed the most potent compounds to be phenylalkenyl and haloalkyl amides 11a and 11e, with IC50 values of 10.5 and 7.2 µM, respectively.
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Antiprotozoarios/síntesis química , Antiprotozoarios/farmacología , Cromonas/síntesis química , Cromonas/farmacología , Leishmania/efectos de los fármacos , Animales , Antiprotozoarios/química , Productos Biológicos/química , Productos Biológicos/farmacología , Línea Celular , Cromonas/química , Ratones , Pruebas de Sensibilidad ParasitariaRESUMEN
Tetrastigma leucostaphylum (TL) is an important ethnic medicine of Bangladesh used to treat diarrhea and dysentery. Hence, current study has been designed to characterize the antidiarrheal (in vivo) and cytotoxic (in vitro) effects of T. leucostaphylum. A crude extract was prepared with methanol (MTL) and further partitioned into n-hexane (NTL), dichloromethane (DTL), and n-butanol (BTL) fractions. Antidiarrheal activity was investigated using castor oil induced diarrhea, enteropooling, and gastrointestinal transit models, while cytotoxicity was evaluated using the brine shrimp lethality bioassay. In antidiarrheal experiments, all doses (100, 200, and 400 mg/kg) of the DTL extract significantly reduced diarrheal stool frequency, volume and weight of intestinal contents, and gastrointestinal motility in mice. Similarly, in the cytotoxicity assay, all extracts exhibited activity, with the DTL extract the most potent (LC50 67.23 µg/mL). GC-MS analysis of the DTL extract identified 10 compounds, which showed good binding affinity toward M3 muscarinic acetylcholine, 5-HT3, Gut inhibitory phosphodiesterase, DNA polymerase III subunit alpha, and UDP-N-acetylglucosamine-1 carboxyvinyltransferase enzyme targets upon molecular docking analysis. Although ADME/T analyses predicted the drug-likeness and likely safety upon consumption of these bioactive compounds, significant toxicity concerns are evident due to the presence of the known phytotoxin, 2,4-di-tert-butylphenol. In summary, T. leucostaphylum showed promising activity, helping to rationalize the ethnomedicinal use and importance of this plant, its safety profile following both acute and chronic exposure warrants further investigation.
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Antidiarreicos/farmacología , Medicina Tradicional , Extractos Vegetales/farmacología , Hojas de la Planta/química , Solventes/química , Vitaceae/química , Animales , Antidiarreicos/metabolismo , Antidiarreicos/uso terapéutico , Motilidad Gastrointestinal/efectos de los fármacos , Ratones , Simulación del Acoplamiento Molecular , Extractos Vegetales/metabolismo , Extractos Vegetales/uso terapéutico , Conformación ProteicaRESUMEN
Ophiorrhiza rugosa var. prostrata is one of the most frequently used ethnomedicinal plants by the indigenous communities of Bangladesh. This study was designed to investigate the antidiarrheal, anti-inflammatory, anthelmintic and antibacterial activities of the ethanol extract of O. rugosa leaves (EEOR). The leaves were extracted with ethanol and subjected to in vivo antidiarrheal screening using the castor oil-induced diarrhea, enteropooling, and gastrointestinal transit models. Anti-inflammatory efficacy was evaluated using the histamine-induced paw edema test. In parallel, in vitro anthelmintic and antibacterial activities were evaluated using the aquatic worm and disc diffusion assays respectively. In all three diarrheal models, EEOR (100, 200 and 400 mg/kg) showed obvious inhibition of diarrheal stool frequency, reduction of the volume and weight of the intestinal contents, and significant inhibition of intestinal motility. Also, EEOR manifested dose-dependent anti-inflammatory activity. Anthelmintic action was deemed significant (P < 0.001) with respect to the onset of paralysis and helminth death. EEOR also resulted in strong zones of inhibition when tested against both Gram-positive and Gram-negative bacteria. GC-MS analysis identified 30 compounds within EEOR, and of these, 13 compounds documented as bioactive showed good binding affinities to M3 muscarinic acetylcholine, 5-HT3, tubulin and GlcN-6-P synthase protein targets in molecular docking experiments. Additionally, ADME/T and PASS analyses revealed their drug-likeness, likely safety upon consumption and possible pharmacological activities. In conclusion, our findings scientifically support the ethnomedicinal use and value of this plant, which may provide a potential source for future development of medicines.
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Diarrea/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Fitoquímicos/administración & dosificación , Fitoquímicos/aislamiento & purificación , Hojas de la Planta/química , Rubiaceae/química , Animales , Antihelmínticos/química , Antihelmínticos/aislamiento & purificación , Antihelmínticos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Simulación por Computador , Diarrea/inducido químicamente , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Inflamación/inducido químicamente , Ratones , Viabilidad Microbiana/efectos de los fármacos , Simulación del Acoplamiento Molecular , Estructura Molecular , Fitoquímicos/química , Fitoquímicos/farmacologíaRESUMEN
Calea uniflora Less. is widely used in southern Santa Catarina (Brazil), but there are no scientific studies which support its use. Then, this study was proposed to determine of the percentage use of C. uniflora in a city of southern Brazil and documentation of the knowledge that the population has about this species. The survey was conducted with semi-structured interviews using a questionnaire applied to 372 participants. In analyzing the results, it was observed that of the 94.1% who recognized C. uniflora, 74.3% utilize it as a medicinal plant and 65.4% of such knowledge originates in childhood, mainly through the family (84.6%). 93% reported using inflorescences macerated in alcohol or rum; this extract is generally used topically for wound healing and muscle pain. Furthermore, some reported using small quantities of this extract orally to treat cold and flu. Regarding effectiveness and safety, 97% stated an improvement in symptoms with the use of the plant, while 98.5% stated that it has no toxicity. In light of these results, future phytochemical, pharmacological and toxicological analyses should be designed in order to ensure rational and safe use of this species.
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Asteraceae , Fitoterapia/estadística & datos numéricos , Plantas Medicinales/química , Brasil , Conocimientos, Actitudes y Práctica en Salud , Humanos , Encuestas y CuestionariosRESUMEN
Carriers are often an essential element of drug delivery, bestowing attributes to their cargo such as biocompatibility, enhanced delivery, extended half-life and efficacy as well as mediating specific targeting at a tissue, cell or intracellular level. Liposomes and lipid-based carriers have been investigated for decades for this purpose, many achieving clinical approval including products such as Doxil® and Myocet™. Large-scale compound screens are routinely carried out in the field of drug discovery; however, less work has been done on harnessing high-throughput methods for carrier material screening. Screening the interaction of drug carriers and materials with cells is particularly critical for the development of emerging therapies, including biomedicines, in order to facilitate the development of safe and efficient drug products. Herein, a range of liposomes of neutral, anionic and cationic charge and others that are surface-modified with mannose residues were screened for cell interaction, toxicity and immune reactivity in THP-1-derived macrophages using a high-throughput format. Liposomes were seen to be efficacious in a concentration-dependent and, for mannosylated liposomes, mannosylated cholesterol linker length-dependent manner.
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Vitamins are essential organic compounds that vary widely in chemical structure and are vital in small quantities for numerous biochemical and biological functions. They are critical for metabolism, growth, development and maintaining overall health. Vitamins are categorised into two groups: hydrophilic and lipophilic. Vitamin K (VK), a lipophilic vitamin, occurs naturally in two primary forms: phylloquinone (VK1), found in green leafy vegetables and algae, and Menaquinones (VK2), present in certain fermented and animal foods and widely formulated in VK supplements. This review explores the possible factors contributing to VK deficiency, including dietary influences, and discusses the pharmacological and therapeutic potential of supplementary VK2, examining recent global clinical studies on its role in treating diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, cardiovascular disease, chronic kidney disease, diabetes, neurodegenerative disorders and cancers. The analysis includes a review of published articles from multiple databases, including Scopus, PubMed, Google Scholar, ISI Web of Science and CNKI, focusing on human studies. The findings indicate that VK2 is a versatile vitamin essential for human health and that a broadly positive correlation exists between VK2 supplementation and improved health outcomes. However, clinical data are somewhat inconsistent, highlighting the need for further detailed research into VK2's metabolic processes, biomarker validation, dose-response relationships, bioavailability and safety. Establishing a Recommended Daily Intake for VK2 could significantly enhance global health.
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A series of phenoxyoxazaphospholidine, phenoxyoxazaphosphinane and benzodioxaphosphininamine sulfides and related cyclic organophosphorus compounds based on the lead anti-tubulin herbicides amiprophos methyl and butamifos were synthesised and evaluated for anti-malarial activity. Of these compounds, while none of the phenoxyoxazaphospholidines, phenoxyoxazaphosphinanes or benzodioxaphosphininamine sulphides were more potent than APM, phosphorothioamidate 30, a dual compound also bearing an aminoquinoline motif, showed promising activity against Plasmodium falciparum (IC50 0.038 µM) and warrants further study.
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Antimaláricos/síntesis química , Compuestos Organofosforados/síntesis química , Plasmodium falciparum/efectos de los fármacos , Sulfuros/síntesis química , Antimaláricos/farmacología , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , Relación Estructura-Actividad , Sulfuros/química , Sulfuros/farmacologíaRESUMEN
Objectives: To understand the experiences of migrant pharmacists in Ireland as they applied for recognition of their qualifications and registration with the national accrediting body. Methods: Semi structured interviews were conducted with eight participants recruited using purposive sampling. Interview transcripts were subject to a phenomenographic study using a stepwise, inductive approach. Results: Data analysis led to the development of a number of categories or descriptions of understanding that provided insight into the ways that participants experienced and conceptualised the phenomenon under study. Five categories of description were identified. These are (1) the migrator, (2) the navigator, (3) the student again, and (4) the registrant. For some, an additional category, (5) the mentee, was experienced. Within these categories, variation in participants' experiences was explored. Conclusions: Participants reported a variety of reasons for migration, and upon embarking on the process, applicants were required to take on a variety of roles, with variation within each role dependent on a number of personal and external factors. Applicants faced personal, administrative, experiential and regulatory hurdles prior to registration, all of which should inform the development of future iterations of this and similar processes.
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Background: Extemporaneous compounding is practiced globally by pharmacists to allow for dispensing of personalised doses of medicinal products not commercially available. Extemporaneous compounding must result in a product which is safe and effective. However, data on formulation and expiry of extemporaneous products may not be readily available. Pharmacists access various resources including compounding databases to obtain information on composition, preparation, and expiry of extemporaneous preparations. Objectives: The aim of this study was to evaluate the type and frequency of extemporaneous compounding in hospital and community pharmacies in the Republic of Ireland (ROI) and to obtain contemporary information on compounding practices and resources used. Methods: All community and hospital pharmacists registered with the Pharmaceutical Society of Ireland, were invited to participate in an on-line survey. The study was approved by the Royal College of Surgeons in Ireland (RCSI) research ethics committee. Results: A total of 202 pharmacists responded to the survey, of which 145 were community-based, 52 hospital-based, and 5 practicing in both. On average, hospital and community pharmacists (n = 138) dispensed <2-10 prescriptions for extemporaneous products per month. Pharmacists reported compounding 13 different types of extemporaneous preparations. Of these, dermatological preparations and oral liquid formulations (OLFs) were most commonly compounded. Extemp.ie, an Irish compounding database, was the most frequently used resource for compounding guidance and product expiry. Conclusions: The results of this study show that extemporaneous compounding is still practiced in hospital and community pharmacies in the ROI. The limited response of 4.6% obtained may reflect that extemporaneous compounding is concentrated in a relatively small number of pharmacies. There remains a clinical need for extemporaneous products in the ROI and extemporaneous compounding continues to be an invaluable skillset for pharmacists.
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Vitamin K1 (VitK1) and Vitamin K2 (VitK2), two important naturally occurring micronutrients in the VitK family, found, respectively, in green leafy plants and algae (VitK1) and animal and fermented foods (VitK2). The present review explores the multiple biological functions of VitK2 from recently published in vitro and in vivo studies, including promotion of osteogenesis, prevention of calcification, relief of menopausal symptoms, enhancement of mitochondrial energy release, hepato- and neuro-protective effects, and possible use in treatment of coronavirus disease. The mechanisms of action associated with these biological effects are also explored. Overall, the findings presented here suggest that VitK, especially VitK2, is an important nutrient family for the normal functioning of human health. It acts on almost all major body systems and directly or indirectly participates in and regulates hundreds of physiological or pathological processes. However, as biological and clinical data are still inconsistent and conflicting, more in-depth investigations are warranted to elucidate its potential as a therapeutic strategy to prevent and treat a range of disease conditions.
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BACKGROUND AND PURPOSE: Objective structured clinical examinations (OSCEs) are widely used, including in licensure examinations. OSCEs assess diverse skills in a structured manner, but can be stressful for students and have a significant organisational burden for faculty. Case-based video OSCE preparation resources were developed for students preparing for a licensure OSCE. The study aimed to examine student engagement, compare scores awarded by students to performances at specific competence standards with faculty scores, and examine usability, usefulness, and acceptability of the video cases. EDUCATIONAL ACTIVITY AND SETTING: Final year pharmacy students (n = 149) enrolled in an integrated master of pharmacy programme in Ireland were invited to participate. Six sets of recorded OSCE-based video cases were developed, comprising multiple recordings of the same case scenario, with each pitched at a different level of performance. Students watched and scored the video cases. Usability, usefulness, and acceptability were evaluated via questionnaire. FINDINGS: One or more video cases were accessed by 70.5% of students. Score ratings awarded by the students, when compared to faculty ratings, showed an overall trend towards inter-rater agreement between students and faculty. Students felt positively in terms of the usability, usefulness, and acceptability of the videos. SUMMARY: Video cases designed to support OSCE preparation for a high-stakes national pharmacy licensure examination were widely used by students and were perceived to be usable, useful, and acceptable. Such video cases may be a feasible alternative to additional mock OSCEs to support student preparation.
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Servicios Farmacéuticos , Farmacia , Estudiantes de Farmacia , Humanos , Docentes , Licencia en FarmaciaRESUMEN
OBJECTIVES: The COVID-19 pandemic triggered rapid, fundamental changes, notably increased remote delivery of primary care. While the impact of these changes on medication safety is not yet fully understood, research conducted before the pandemic may provide evidence for possible consequences. To examine the published literature on medication safety incidents associated with the remote delivery of primary care, with a focus on telemedicine and electronic prescribing. METHODS: A rapid review was conducted according to the Cochrane Rapid Reviews Methods Group guidance. An electronic search was carried out on Embase and Medline (via PubMed) using key search terms 'medication error', 'electronic prescribing', 'telemedicine' and 'primary care'. Identified studies were synthesised narratively; reported medication safety incidents were categorised according to the WHO Conceptual Framework for the International Classification for Patient Safety. KEY FINDINGS: Fifteen studies were deemed eligible for inclusion. All 15 studies reported medication incidents associated with electronic prescribing; no studies were identified that reported medication safety incidents associated with telemedicine. The most commonly reported medication safety incidents were 'wrong label/instruction' and 'wrong dose/strength/frequency'. The frequency of medication safety incidents ranged from 0.89 to 81.98 incidents per 100 electronic prescriptions analysed. SUMMARY: This review of medication safety incidents associated with the remote delivery of primary care identified common incident types associated with electronic prescriptions. There was a wide variation in reported frequencies of medication safety incidents associated with electronic prescriptions. Further research is required to determine the impact of the COVID-19 pandemic on medication safety in primary care, particularly the increased use of telemedicine.
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COVID-19 , Prescripción Electrónica , Humanos , Pandemias , Seguridad del Paciente , Errores de MedicaciónRESUMEN
BACKGROUND: Plasma neuronal-derived extracellular vesicles (NDEV) contain proteins of pathological, diagnostic, and therapeutic relevance. OBJECTIVE: We investigated the associations of six plasma NDEV markers with Alzheimer's disease (AD) severity, cognition and functioning, and changes in these biomarkers after Cerebrolysin®, donepezil, and a combination therapy in AD. METHODS: Plasma NDEV levels of Aß42, total tau, P-T181-tau, P-S393-tau, neurogranin, and REST were determined in: 1) 116 mild to advanced AD patients and in 20 control subjects; 2) 110 AD patients treated with Cerebrolysin®, donepezil, or combination therapy in a randomized clinical trial (RCT). Samples for NDEV determinations were obtained at baseline in the NDEV study and at baseline and study endpoint in the RCT. Cognition and functioning were assessed at the same time points. RESULTS: NDEV levels of Aß42, total tau, P-T181-tau, and P-S393-tau were higher and those of neurogranin and REST were lower in mild-to-moderate AD than in controls (pâ<â0.05 to pâ<â0.001). NDEV total tau, neurogranin, and REST increased with AD severity (pâ<â0.05 to pâ<â0.001). NDEV Aß42 and P-T181-tau correlated negatively with serum BDNF (pâ<â0.05), and total-tau levels were associated to plasma TNF-α (pâ<â0.01) and cognitive impairment (pâ<â0.05). Combination therapy reduced NDEV Aß42 with respect to monotherapies (pâ<â0.05); and NDEV total tau, P-T181-tau, and P-S396-tau were decreased in Cerebrolysin-treated patients compared to those on donepezil monotherapy (pâ<â0.05). CONCLUSION: The present results demonstrate the utility of NDEV determinations of pathologic and synaptic proteins as effective AD biomarkers, as markers of AD severity, and as potential tools for monitoring the effects of anti-AD drugs.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Vesículas Extracelulares , Humanos , Enfermedad de Alzheimer/diagnóstico , Donepezilo/uso terapéutico , Neurogranina , Proteínas tau/metabolismo , Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/diagnóstico , Biomarcadores , Vesículas Extracelulares/metabolismo , Fragmentos de Péptidos/metabolismoRESUMEN
The impact of the COVID-19 pandemic on pharmacy education worldwide has been immense, affecting students, educators and regulatory agencies. Pharmacy programmes have had to rapidly adapt in their delivery of education, maintaining standards while also ensuring the safety of all stakeholders. In this commentary, we describe the challenges, compromises and solutions adopted by our institution throughout the pandemic, the lessons learnt, adaptive measures taken, and strategies to develop and future-proof our curricula.
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COVID-19 , Educación en Farmacia , Farmacia , Estudiantes de Farmacia , COVID-19/epidemiología , Curriculum , Humanos , PandemiasRESUMEN
Calea pinnatifida (R. Br.) Less. is a plant of Brazilian folk medicine. We evaluated the influence of environmental factors on the chemical profile of C. pinnatifida collected during the winter season. C. pinnatifida leaves, alongside soil samples, were collected from two sites of different altitude. Plant samples were sequentially extracted, while soil samples were subject to compositional analysis. Plant extracts were compared using HPTLC-UV, using chemometric analyses to compare samplings harvested at both altitudes. Two marker metabolites, calein A (1) and acetylportentol (2), were isolated from samples collected at the respective altitudes. The differing metabolic profiles observed may be a result of the influence of environmental factors.
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Asteraceae , Plantas Medicinales , Altitud , Brasil , Extractos Vegetales , Hojas de la Planta , SueloRESUMEN
Introduction: The COVID-19 pandemic has had a profound impact on the delivery of primary care around the world. In Ireland, the use of technologies such as virtual consultations and the electronic transfer of prescriptions became widespread in order to deliver care to patients while minimising infection risk. The impact of these changes on medication safety is not yet known. Objectives: The aims of this survey study were to investigate 1) the changes that have occurred in Irish primary care since the start of the COVID-19 pandemic and 2) the impact of these changes on medication safety. Methods: Anonymous, online surveys were distributed to general practitioners (GPs) and pharmacists from August-September 2021. Surveys contained quantitative (multiple-choice, Likert scale) and qualitative (free-text) questions concerning workflow changes, medication safety incidents and near misses, and GP/pharmacist perspectives on medication safety and COVID-19. Reported medication safety incidents and near misses were categorised according to the WHO Conceptual Framework for the International Classification for Patient Safety. Results: In total, there were 251 responses to the survey, comprising of 211 pharmacists and 40 GPs. The most significant workflow changes during the pandemic were the widespread use of a secure clinical email service (Healthmail) that facilitates electronic prescription transfer and communication (75.3% of respondents) and the increased use of telephone consultations (49%). Overall, Healthmail was widely perceived to have had a positive impact on medication safety. Most GPs did not perceive a change in the frequency of medication safety incidents during the pandemic, while most pharmacists reported a slight increase in incidents. Survey participants highlighted pressure, patient expectations, and patient monitoring as significant challenges encountered during the pandemic. Conclusions: During the pandemic, a number of significant changes occurred in primary care in Ireland, particularly involving communication of healthcare information, with varying impacts on workflow and medication safety. Future research should focus on the optimisation of electronic prescribing and telemedicine services in Ireland, patient perspectives on the changes in primary care, and interventions to improve medication safety in primary care.
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Each stereoisomer of 3-[methyl(1,2,3,4-tetrahydro-2-naphthalenyl)amino]-1-indanone, 1a-d, was prepared and evaluated in vitro for its ability to prevent mediator release induced by different degranulating agents from rodent mast cells and also in vivo against passive cutaneous anaphylaxis. The manner in which the stereoisomers prevented direct membrane activation was found to be highly dependent on the stereochemistry of the individual isomers. Stereoisomer 1b was the most active isomer in vivo, exhibiting superior activity to disodium cromoglycate.
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2-Naftilamina/análogos & derivados , Indanos/síntesis química , Mastocitos/efectos de los fármacos , 2-Naftilamina/síntesis química , 2-Naftilamina/química , 2-Naftilamina/farmacología , Animales , Cristalografía por Rayos X , Histamina/metabolismo , Indanos/química , Indanos/farmacología , Ratones , Conformación Molecular , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Estereoisomerismo , PorcinosRESUMEN
A series of phosphoramidate and phosphorothioamidate compounds based on the lead antitubulin herbicidal agents amiprophos methyl (APM) and butamifos were synthesised and evaluated for antimalarial activity. Of these compounds, phosphorothioamidates were more active than their oxo congeners and the nature of both aryl and amido substituents influenced the desired activity. The most active compound was 46, O-ethyl-O-(2-methyl-4-nitrophenyl)-N-cyclopentyl phosphorothioamidate, which was more effective than the lead compound.
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Amidas/química , Amidas/farmacología , Antimaláricos/química , Antimaláricos/farmacología , Nitrobencenos/química , Nitrobencenos/farmacología , Compuestos Organotiofosforados/química , Compuestos Organotiofosforados/farmacología , Ácidos Fosfóricos/química , Ácidos Fosfóricos/farmacología , Plasmodium falciparum/efectos de los fármacos , Amidas/síntesis química , Antimaláricos/síntesis química , Humanos , Malaria Falciparum/tratamiento farmacológico , Nitrobencenos/síntesis química , Compuestos Organotiofosforados/síntesis química , Ácidos Fosfóricos/síntesis química , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologíaRESUMEN
Introduction: Cognitive deficits in people with schizophrenia (PWS) are a major predictor of disability and functioning, yet the underlying pathophysiology remains unclear. A possible role of amyloid and tau biomarkers (hallmarks of Alzheimer's disease) is still speculative in schizophrenia. Exosomes or extracellular vesicles, involved with cell-to-cell communication and waste removal, can be used to assay brain-based proteins from peripheral blood. To our knowledge, this is the first study of exosomal amyloid and tau protein levels in PWS. Methods: This cross-sectional study included 60 PWS and 60 age- and sex-comparable non-psychiatric comparison subjects (NCs), age range 26-65 years. Assessments of global cognitive screening, executive functioning, psychopathology, and physical measures were conducted. Exosomes were extracted and precipitated from fasting plasma and identified as neuron-derived exosomes (NDEs) or astrocyte-derived exosomes (ADEs). Human-specific ELISAs were used to assay levels of amyloid-beta 1-42 (Aß42), amyloid-beta 1-40 (Aß40), and phosphorylated T181 tau (P-T181-tau). Plasma assays for aging biomarkers (C-reactive protein and F2-isoprostanes) were also performed. Results: ADE-Aß42 levels were higher in PWS compared to NCs, though the other exosomal markers were similar between the two groups. Higher ADE-P-T181-tau levels were associated with worse executive functioning. Among PWS, higher ADE-P-T181-tau levels were associated with less severe negative symptoms and increased F2-isoprostane levels. Astrocyte-derived Aß marker levels were sensitive and specific in differentiating between diagnostic groups. Among PWS, Aß40 levels differed most by exosomal origin. Discussion: Exosomal markers may provide novel insights into brain-based processes (e.g., aging, oxidative stress) from peripheral blood samples.