Protective effects of irbesartan against neurodegeneration in APP/PS1 mice: Unraveling its triple anti-apoptotic, anti-inflammatory and anti-oxidant action.

Alzheimer's disease (AD) involves a complex interplay between amyloid-β plaques, oxidative stress, neuroinflammation and apoptosis, suggesting that multi-target therapies may be more effective than single-target treatments. Angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) have shown protective effects against AD in hypertensive patients. However, those poor blood-brain barrier (BBB) permeability exhibit limited efficacy in neurodegenerative disorders.

Potentially Inappropriate Prescribing to Older Patients Admitted to Units for Integrated Continuous Care: Application of STOPP/START Criteria.

: Potentially inappropriate medications (PIMs) and potential prescription omissions (PPOs) have been widely explored, but few studies focused on patients aged 75 years and over. This study was planned to explore the demographic and clinical characteristics of the older patients admitted to Units for Integrated Continuous Care, and to assess the prevalence and potential predictors of PIMs and PPOs. : An observational, retrospective, and multicenter study was performed on 135 patients aged 75 years or older (i.

Phenolic Acids from Fruit By-Products as Therapeutic Agents for Metabolic Syndrome: A Review.

The cultivation and processing of fruits generate a wide range of by-products (e.g., pulp, seeds, pomace, leaves, and stems), which are often underutilized despite being rich sources of phenolic compounds with well-documented bioactive properties.

Chronopharmacokinetics of the antidepressant paroxetine: An in vitro and in vivo approach.

The circadian rhythm influences homeostatic functions such as sleep, physical activity and food intake as well as pharmacotherapy, namely pharmacokinetics. To investigate the impact of the circadian rhythm on the pharmacokinetics of paroxetine, in vitro synchronized permeability studies were carried out in a tri-culture blood-brain barrier model. Paroxetine demonstrated lower apparent permeability when the cells were incubated at 24 h post-synchronization than at 36 h.

Pharmacokinetics of Non-Psychotropic Phytocannabinoids.

Cannabinoids are widely recognized for their potential therapeutic effects, making them significant and valuable candidates for medical research and applications across various fields. This review aims to analyze the pharmacokinetics of Cannabidiol (CBD), Cannabigerol (CBG), and Cannabichromene (CBC), along with their corresponding acidic forms, Cannabidiolic acid (CBDA), Cannabigerolic acid (CBGA), and Cannabichromenic acid (CBCA). Among these cannabinoids, CBD is the most extensively studied.

Population pharmacokinetics of levetiracetam in patients diagnosed with refractory epilepsy: A real-world study.

Objectives: Levetiracetam is a widely used antiseizure drug in patients with refractory epilepsy due to its specific mechanism of action. This study aimed to develop and validate a population pharmacokinetic model (PopPK) to optimize levetiracetam dosing in patients with refractory epilepsy.

Methods: A total of 256 plasma concentrations of levetiracetam, obtained from 135 patients, were employed for PopPK model development, applying a nonlinear mixed-effects modeling methodology.

A new population pharmacokinetic model for dosing optimization of zonisamide in patients with refractory epilepsy.

Zonisamide exhibits significant pharmacokinetic variability, demanding for the development of population pharmacokinetic (PopPK) models to identify key factors influencing drug disposition. This study aimed to develop and validate a PopPK model to optimize zonisamide posology in patients with refractory epilepsy. A total of 114 plasma concentrations of zonisamide, obtained from 64 patients, were used for PopPK model development, employing the nonlinear mixed-effects modelling approach.

Dendritic cells in triple-negative breast cancer: From pathophysiology to therapeutic applications.

Breast cancer is the second most commonly diagnosed cancer in women and the fifth leading cause of cancer-related deaths worldwide. It is a highly heterogeneous disease, consisting of multiple subtypes that vary significantly in clinical characteristics and survival outcomes. Triple-negative breast cancer (TNBC) is a particularly aggressive and challenging subtype of breast cancer.

The impact of extract on pharmacokinetics of phenytoin in rats.

Epilepsy patients are at a higher risk of developing overweight and obesity. Given the thermogenic properties of (Guarana), this study aimed to evaluate a potential pharmacokinetic interaction between extract and phenytoin in rats. Two pharmacokinetic studies were developed with and phenytoin: a coadministration and a pre-treatment study.

Unveiling the potential of intranasal delivery of renin-angiotensin system drugs: Insights on the pharmacokinetics of irbesartan.

The therapeutic interest of renin-angiotensin system (RAS) drugs for the treatment of neuroinflammation has been recently acknowledged. Nevertheless, most of them display limited passage across the blood-brain barrier (BBB). Therefore, this study investigated the potential of intranasal (IN) delivery of six RAS drugs to circumvent the BBB and attain the brain, envisioning its future use in central nervous system (CNS) neuroinflammatory diseases, such as Alzheimer's disease (AD).

The potential of exosomes as a new therapeutic strategy for glioblastoma.

Glioblastoma (GBM) stands for the most common and aggressive type of brain tumour in adults. It is highly invasive, which explains its short rate of survival. Little is known about its risk factors, and current therapy is still ineffective.

Blood brain barrier dysfunction in healthy aging and dementia: Why, how, what for?

The blood brain barrier (BBB) is an indispensable structure that maintains the central nervous system (CNS) microenvironment for a correct neuronal function. It is composed by highly specialized microvessels, surrounded by astrocytes, pericytes, neurons and microglia cells, which tightly control the influx and efflux of substances to the brain parenchyma. During aging, the BBB becomes impaired, and it may contribute to the development of neurodegenerative and neurological disorders including Alzheimer's disease and other dementias.

Development and validation of an HPLC-DAD method for the quantification of cannabigerol, cannabidiol, cannabinol and cannabichromene in human plasma and mouse matrices.

Cannabigerol, cannabidiol, cannabinol and cannabichromene are non-psychoactive phytocannabinoids, highly present in , for which numerous therapeutical applications have been described. However, additional pre-clinical and clinical data, including toxicopharmacokinetic and pharmacodynamic studies, remain required to support their use in clinical practice and new therapeutic applications. To support these studies, a new high performance liquid chromatography technique (HPLC) with diode-array detection (DAD) was developed and validated to quantify these cannabinoids in human plasma and mouse matrices.

Antioxidant activity of the main phenolics found in red fruits: An in vitro and in silico study.

The current study analysed the antioxidant capacity of the main phenolics found in red fruits. In total, there were analysed the antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl radical, nitric oxide and superoxide radicals (DPPH, NO and O, respectively) of 23 phenolics. Regarding DPPH, anthocyanins, (-)-epicatechin and kaempferol 3-O-rutinoside were the most active, while isorhamnetin 3-O-glucoside was the least active.

Krüppel-like factors: potential roles in blood-brain barrier dysfunction and epileptogenesis.

Epilepsy is a chronic and debilitating neurological disorder, known for the occurrence of spontaneous and recurrent seizures. Despite the availability of antiseizure drugs, 30% of people with epilepsy experience uncontrolled seizures and drug resistance, evidencing that new therapeutic options are required. The process of epileptogenesis involves the development and expansion of tissue capable of generating spontaneous recurrent seizures, during which numerous events take place, namely blood-brain barrier (BBB) dysfunction, and neuroinflammation.

Intranasal delivery of paroxetine: A preclinical study on pharmacokinetics, depressive-like behaviour, and neurochemical sex differences.

Treatment of major depressive disorder remains a major unmet clinical need. Given the advantages of intranasal administration for targeted brain delivery, the present study aimed at investigating the pharmacokinetics of paroxetine, after its intranasal instillation and assessing its potential therapeutic effect on female and male mice subjected to unpredictable chronic mild stress (UCMS) protocol. IN administration revealed direct nose-to-brain paroxetine delivery but dose- and sex-dependent differences.

Patients' Characterization, Pattern of Medication Use, and Factors Associated with Polypharmacy: A Cross-Sectional Study Focused on Eight Units of the Portuguese National Network for Long-Term Integrated Care.

The Portuguese National Network for Long-term Integrated Care (RNCCI) comprises several Units for Integrated Continuous Care (UCCIs) that provide medical, nursing, and rehabilitation care. This study aimed to evaluate the demographic and medical characteristics of patients admitted to the RNCCI, their patterns of medication use, and factors associated with polypharmacy. An observational, retrospective, cross-sectional, multicenter study was performed.

Diversity of Culture Microorganisms from Portuguese Sweet Cherries.

Consumers today seek safe functional foods with proven health-promoting properties. Current evidence shows that a healthy diet can effectively alleviate oxidative stress levels and reduce inflammatory markers, thereby preventing the occurrence of many types of cancer, hypertension, and cardiovascular and neurological pathologies. Nevertheless, as fruits and vegetables are mainly consumed fresh, they can serve as vectors for the transmission of pathogenic microorganisms associated with various disease outbreaks.

Intranasal administration of sertraline ensures sustained brain delivery and antidepressant effect in a mouse model of depression.

The pursuit of more potent and efficacious antidepressant therapies is of utmost significance. Herein, the intranasal (IN) route was investigated for sertraline brain delivery, encompassing a comparative pharmacokinetic study after a single-dose administration to mice by IN, intravenous (IV) (4.87 mg/kg) and oral (10 mg/kg) routes, and an efficacy/toxicity study to explore the therapeutic effect in mice subjected to the unpredictable chronic mild stress (UCMS) protocol.

A physiological approach to renal clearance: From premature neonates to adults.

Aims: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance.

Methods: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine.

Artificial Dendritic Cells: A New Era of Promising Antitumor Immunotherapy.

The accelerated development of antitumor immunotherapies in recent years has brought immunomodulation into the spotlight. These include immunotherapeutic treatments with dendritic cell (DC)-based vaccines which can elicit tumor-specific immune responses and prolong survival. However, this personalized treatment has several drawbacks, including being costly, labor-intensive, and time consuming.

Under the umbrella of depression and Alzheimer's disease physiopathology: Can cannabinoids be a dual-pleiotropic therapy?

Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60-80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiopathological mechanisms.

Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy.

Perampanel is a promising antiepileptic drug (AED) for refractory epilepsy treatment due to its innovative mechanism of action. This study aimed to develop a population pharmacokinetic (PopPK) model to be further used in initial dose optimization of perampanel in patients diagnosed with refractory epilepsy. A total of seventy-two plasma concentrations of perampanel obtained from forty-four patients were analyzed through a population pharmacokinetic approach by means of nonlinear mixed effects modeling (NONMEM).

Intranasal Microemulsion as an Innovative and Promising Alternative to the Oral Route in Improving Stiripentol Brain Targeting.

Stiripentol (STP) is a new-generation antiepileptic only available for oral administration. However, it is extremely unstable in acidic environments and undergoes gastrointestinal slow and incomplete dissolution. Thus, STP intranasal (IN) administration might overcome the high oral doses required to achieve therapeutic concentrations.