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Chemotherapy-induced neuropathic pain (CINP), a condition with unmet treatment needs, affects over half of cancer patients treated with chemotherapeutics. Researchers have recently focused on the endocannabinoid system because of its critical role in regulating our bodies' most important functions, including pain. We used in vitro and in vivo methods to determine the toxicity profile of a synthetic cannabinoid, JWH-182, and whether it could be potentially effective for CINP alleviation. In vitro, we evaluated JWH-182 general toxicity, measuring fibroblast viability treated with various concentrations of compound, and its neuroprotection on dorsal root ganglion neurons treated with paclitaxel. In vivo, we performed an evaluation of acute and 28-day repeated dose toxicity in mice, with monitoring of health status and a complete histopathological examination. Finally, we evaluated the efficacy of JWH-182 on a CINP model in mice using specific pain assessment tests. JWH-182 has an acceptable toxicity profile, in both, in vitro and in vivo studies and it was able to significantly reduce pain perception in a CINP model in mice. However, the translation of these results to the clinic needs further investigation.
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Canabinoides , Neuralgia , Animais , Neuralgia/tratamento farmacológico , Neuralgia/induzido quimicamente , Camundongos , Canabinoides/farmacologia , Modelos Animais de Doenças , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Masculino , Humanos , Paclitaxel/efeitos adversos , Paclitaxel/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismoRESUMO
BACKGROUND: The long-term consumption of junk food products can lead to nutritional and metabolic imbalances, especially when it is associated with a lack of physical activity and the consumption of alcohol or other high-calorie products. METHODS: The evaluation of junk food consumption among teenagers and young people in Romania was carried out with the help of a cross-sectional study based on a questionnaire. RESULTS: A total number of 1017 respondents participated in this study, comprising 470 males and 547 females aged between 16 and 25 years. Although the majority of young people fell into the normal-weight category (607 of them, p < 0.0001), some aspects can be noted that in the long term can produce a series of nutritional imbalances: an increased tendency toward sedentarism, with 553 (p = 0.613) of the respondents declaring that they performed sports rarely or not at all, and a tendency toward relatively high consumption of foods high in calories (fast food products and especially fried potatoes, hamburgers, shawarma, pastries, and snacks, along with sweetened drinks and even alcoholic beverages). The respondents participating in this study even indicated a perceived addiction to the consumption of certain products: coffee (50.48%), fried potatoes (38.9%), hamburgers (37.05%), shawarma (31.65%), and snacks (30.08%). Many of these products are rich in calories, saturated fat, and even trans fat. CONCLUSIONS: This study highlights a series of aspects that can have long-term negative effects related to the excess weight associated with other imbalances: consumption preferences among young people for hypercaloric fast food products, sweetened drinks associated with reduced physical activity, and even the development of some forms of food addictions for a series of hypercaloric foods.
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Fast Foods , Comportamento Alimentar , Estilo de Vida , Humanos , Romênia , Masculino , Feminino , Adolescente , Adulto Jovem , Estudos Transversais , Adulto , Fast Foods/estatística & dados numéricos , Ingestão de Energia , Dieta/estatística & dados numéricos , Inquéritos e Questionários , Comportamento Sedentário , Exercício FísicoRESUMO
Despite decades of rigorous research and numerous clinical trials, Alzheimer's disease (AD) stands as a notable healthcare challenge of this century, with effective therapeutic solutions remaining elusive. Recently, the endocannabinoid system (ECS) has emerged as an essential therapeutic target due to its regulatory role in different physiological processes, such as neuroprotection, modulation of inflammation, and synaptic plasticity. This aligns with previous research showing that cannabinoid receptor ligands have the potential to trigger the functional structure of neuronal and brain networks, potentially impacting memory processing. Therefore, our study aims to assess the effects of prolonged, intermittent exposure (over 90 days) to JWH-133 (0.2 mg/kg) and an EU-GMP certified Cannabis sativa L. (Cannabixir® Medium Flos, 2.5 mg/kg) on recognition memory, as well as their influence on brain metabolism and modulation of the expanded endocannabinoid system in APP/PS1 mice. Chronic therapy with cannabinoid receptor ligands resulted in reduced anxiety-like behavior and partially reversed the cognitive deficits. Additionally, a reduction was observed in both the number and size of Aß plaque deposits, along with decreased cerebral glucose metabolism, as well as a decline in the expression of mTOR and CB2 receptors. Furthermore, the study revealed enlarged astrocytes and enhanced expression of M1 mAChR in mice subjected to cannabinoid treatment. Our findings highlight the pivotal involvement of the extended endocannabinoid system in cognitive decline and pathological aspects associated with AD, presenting essential preclinical evidence to support the continued exploration and assessment of cannabinoid receptor ligands for AD treatment.
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BACKGROUND: Alzheimer's disease (AD), along with other neurodegenerative disorders, remains a challenge for clinicians, mainly because of the incomplete knowledge surrounding its etiology and inefficient therapeutic options. Considering the central role of amyloid beta (Aß) in the onset and evolution of AD, Aß-targeted therapies are among the most promising research directions. In the context of decreased Aß elimination from the central nervous system in the AD patient, the authors propose a novel therapeutic approach based on the "Cerebrospinal Fluid Sink Therapeutic Strategy" presented in previous works. This article aims to demonstrate the laborious process of the development and testing of an effective nanoporous ceramic filter, which is the main component of an experimental device capable of filtrating Aß from the cerebrospinal fluid in an AD mouse model. METHODS: First, the authors present the main steps needed to create a functional filtrating nanoporous ceramic filter, which represents the central part of the experimental filtration device. This process included synthesis, functionalization, and quality control of the functionalization, which were performed via various spectroscopy methods and thermal analysis, selectivity measurements, and a biocompatibility assessment. Subsequently, the prototype was implanted in APP/PS1 mice for four weeks, then removed, and the nanoporous ceramic filter was tested for its filtration capacity and potential structural damages. RESULTS: In applying the multi-step protocol, the authors developed a functional Aß-selective filtration nanoporous ceramic filter that was used within the prototype. All animal models survived the implantation procedure and had no significant adverse effects during the 4-week trial period. Post-treatment analysis of the nanoporous ceramic filter showed significant protein loading, but no complete clogging of the pores. CONCLUSIONS: We demonstrated that a nanoporous ceramic filter-based system that filtrates Aß from the cerebrospinal fluid is a feasible and safe treatment modality in the AD mouse model. The presented prototype has a functional lifespan of around four weeks, highlighting the need to develop advanced nanoporous ceramic filters with anti-biofouling properties to ensure the long-term action of this therapy.
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A new trend in the use of indole alkaloids from natural products is the preparation of topical pharmaceutical formulations with applications in the field of regenerative medicine. These formulations can be characterized through the ease of administration, the proven healing action of indole alkaloids, the protection of skin lesions, and the assurance of oxygen permeability. Based on the numerous benefits that indole compounds extracted from the Vinca minor plant show externally, the purpose of this study was to develop new semi-solid biocomposites for topical application obtained from hydroalcoholic macerates of 40%, 70%, and 96% concentrations from the stems and leaves of the Vinca minor L. plant from the Dobrogea area. A total of 12 pharmaceutical formulations (named P1-P12) were prepared for which the physicochemical properties, pH, thermal stability, spreading capacity, and rheological behavior were determined. The optimal formulas with antioxidant and antimicrobial capacity were evaluated and determined (P3, P4, P9, and P10). Antioxidant activity was elicited using the photochemiluminescence method. The microorganisms used for the evaluation of antimicrobial activity were Gram-positive Staphylococcus aureus (ATCC 25923), Gram-negative Escherichia coli (ATCC 25922), and a fungal species, Candida albicans (ATCC 900288). The study of the rheological profile for the obtained composites revealed Newtonian, pseudoplastic, and thixotropic fluid behaviors. Following determinations using the photochemiluminescence method, the best antioxidant activity was obtained in the P3 and P9 preparations. The results of the antimicrobial analysis confirmed that both the leaves and the stems of the Vinca minor plant represent a valuable source of antibacterial substances, and the biocomposites analyzed may represent an alternative in the realization of new pharmaceutical preparations with topical applications based on hydroalcoholic macerates obtained from the Vinca minor plant.
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Anti-Infecciosos , Vinca , Vinca/química , Antioxidantes/farmacologia , Alcaloides Indólicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antibacterianos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
The incidence of neurodegenerative diseases, such as Alzheimer's disease (AD), is continuously growing worldwide, which leads to a heavy economic and societal burden. The lack of a safe and effective causal therapy in cognitive decline is an aggravating factor and requires investigations into the repurposing of commonly used drugs. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new and efficient class of hypoglycemic drugs and, due to their pleiotropic effects, have indications that go beyond diabetes. There is emerging data from murine studies that SGLT2i can cross the blood-brain barrier and may have neuroprotective effects, such as increasing the brain-derived neurotrophic factor (BDNF), reducing the amyloid burden, inhibiting acetylcholinesterase (AChE) and restoring the circadian rhythm in the mammalian target of rapamycin (mTOR) activation. The current study investigates the effect of an SGLT2i and donepezil, under a separate or combined 21-day treatment on AD-relevant behaviors and brain pathology in mice. The SGLT2i canagliflozin was found to significantly improve the novelty preference index and the percentage of time spent in the open arms of the maze in the novel object recognition and elevated plus maze test, respectively. In addition, canagliflozin therapy decreased AChE activity, mTOR and glial fibrillary acidic protein expression. The results also recorded the acetylcholine M1 receptor in canagliflozin-treated mice compared to the scopolamine group. In the hippocampus, the SGLT2i canagliflozin reduced the microgliosis and astrogliosis in males, but not in female mice. These findings emphasize the value of SGLT2i in clinical practice. By inhibiting AChE activity, canagliflozin represents a compound that resembles AD-registered therapies in this respect, supporting the need for further evaluation in dementia clinical trials.
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Generally, NSAIDs are weakly soluble in water and contain both hydrophilic and hydrophobic groups. One of the most widely used NSAIDs is ibuprofen, which has a poor solubility and high permeability profile. By creating dynamic, non-covalent, water-soluble inclusion complexes, cyclodextrins (CDs) can increase the dissolution rate of low aqueous solubility drugs, operating as a drug delivery vehicle, additionally contributing significantly to the chemical stability of pharmaceuticals and to reducing drug-related irritability. In order to improve the pharmacological and pharmacokinetics profile of ibuprofen, new thiazolidin-4-one derivatives of ibuprofen (4b, 4g, 4k, 4m) were complexed with ß-CD, using co-precipitation and freeze-drying. The new ß-CD complexes (ß-CD-4b, ß-CD-4g, ß-CD-4k, ß-CD-4m) were characterized using scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction and a phase solubility test. Using the AutoDock-VINA algorithm included in YASARA-structure software, we investigated the binding conformation of ibuprofen derivatives to ß-CD and measured the binding energies. We also performed an in vivo biological evaluation of the ibuprofen derivatives and corresponding ß-CD complexes, using analgesic/anti-inflammatory assays, as well as a release profile. The results support the theory that ß-CD complexes (ß-CD-4b, ß-CD-4g, ß-CD-4k, ß-CD-4m) have a similar effect to ibuprofen derivatives (4b, 4g, 4k, 4m). Moreover, the ß-CD complexes demonstrated a delayed release profile, which provides valuable insights into the drug-delivery area, focused on ibuprofen derivatives.
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The Renin-Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer's dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and renin inhibitors in AD. ACEIs, commonly used for hypertension, show promise in AD by reducing angiotensin (Ang) II levels. This reduction is significant as Ang II contributes to neuroinflammation, oxidative stress, and ß-amyloid (Aß) accumulation, all implicated in AD pathogenesis. ARBs, known for vasodilation, exhibit neuroprotection by blocking Ang II receptors, improving cerebral blood flow and cognitive decline in AD models. Renin inhibitors offer a novel approach by targeting the initial RAS step, displaying anti-inflammatory and antioxidant effects that mitigate AD degeneration. Preclinical studies demonstrate RAS regulation's favorable impact on neuroinflammation, neuronal damage, cognitive function, and Aß metabolism. Clinical trials on RAS modulators in AD are limited, but with promising results, ARBs being more effective that ACEIs in reducing cognitive decline. The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies.
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The range of non-alcoholic drinks is very varied both from a compositional point of view and from a caloric and nutritional point of view. The excessive consumption of sweetened non-alcoholic beverages represents an important risk factor for health, especially when it is accompanied by an unbalanced diet and a disordered lifestyle. In order to evaluate the consumption of non-alcoholic beverages correlated with the evaluation of the main lifestyle factors that can affect the state of health among Romanians, a cross-sectional observational study was carried out based on a questionnaire. The results of the study indicate that among the most consumed non-alcoholic drinks are coffee and sweetened carbonated and non-carbonated drinks, which are indicated as being responsible for the development of consumption addictions: 44% for coffee, 16.5% for sweetened or tonic carbonated drinks and 12% for sweetened non-carbonated drinks. Considering that the consumption of coffee is usually associated with sweeteners, there is a risk of excessive caffeine and caloric intake in a context where a lack of exercise predominates (59.98%) among respondents declaring that they do sports rarely or not at all, which can lead, in the long term, to the appearance of imbalances either of a psycho-emotional nature or of a metabolic nature. A significant link was found between sports activity and the environment in which they work (χ2 = 51.33, p = 0.05). Respondents with a daily activity that involves movement (working outdoors, working on a construction site) are also those who usually do sports, while 60.67% of the respondents who work a lot in front of the computer declared that they do sports very rarely or not at all. Reducing the excessive consumption of sweetened drinks can be achieved through an appropriate consumption of water and fruits and by intensifying physical activity as a way of counterbalancing the excess caloric intake.
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Bebidas , Café , Café/efeitos adversos , Estudos Transversais , Romênia , Bebidas/efeitos adversos , Cafeína , FrutasRESUMO
Premature aging and degradative processes are mainly generated by unhealthy habits and an unbalanced diet. Quality of food and lifestyle are important factors in sano-genesis. Many imbalances and ailments have their origin in the adoption of an unbalanced diet and a disordered lifestyle. With the help of a transversal study carried out on the basis of a questionnaire, the consumption of junk food products among the population of Romania was evaluated; at the same time, an evaluation of the characteristics of the associated diet, as well as a series of lifestyle components (quality of rest, physical activity, evaluation of the state of health) was carried out. The data collected and processed indicate an increased tendency to consume junk food products in the 18-23 age group, and especially among obese respondents. Female respondents show a lower tendency toward an increased consumption of junk food products (OR = 0.703, 95% CI)-0.19-0.95, p = 0.011) compared to male respondents. The most consumed junk food products are fried potatoes (46.2%) and pastries (41.4%). Junk food products that show an increased tendency toward consumption addiction are fried potatoes (13.8%), sweets (12.4%), pastry products (11.1%), and sweetened drinks (11.2%). The poor quality of food from a nutritional point of view, and reduced physical activity, are reflected in the varied range of problems faced by the respondents: states of fatigue (62.4%), nervousness (37.5%), depression, anxiety, emotional eating, etc.
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Comportamento Aditivo , Etnicidade , Feminino , Masculino , Humanos , Romênia/epidemiologia , Ansiedade , Transtornos de AnsiedadeRESUMO
As some of the renin-angiotensin-aldosterone system (RAAS)-dependent mechanisms underlying the cognitive performance modulation could include oxidative balance alterations, in this study we aimed to describe some of the potential interactions between RAAS modulators (Losartan and Ramipril) and oxidative stress in a typical model of memory impairment. In this study, 48 white male Swiss mice were divided into six groups and received RAAS modulators (oral administration Ramipril 4 mg/kg, Losartan 20 mg/kg) and a muscarinic receptors inhibitor (intraperitoneal injection scopolamine, 0.5 mg/kg) for 8 consecutive days. Then, 24 h after the last administration, the animals were euthanized and whole blood and brain tissues were collected. Biological samples were then processed, and biochemical analysis was carried out to assess superoxide dismutase and glutathione activities and malondialdehyde concentrations. In the present experimental conditions, we showed that RAAS modulation via the angiotensin-converting enzyme inhibition (Ramipril) and via the angiotensin II receptor blockage (Losartan) chronic treatments could lead to oxidative stress modulation in a non-selective muscarinic receptors blocker (scopolamine) animal model. Our results showed that Losartan could exhibit a significant systemic antioxidant potential partly preventing the negative oxidative effects of scopolamine and a brain antioxidant potential, mainly by inhibiting the oxidative-stress-mediated cellular damage and apoptosis. Ramipril could also minimize the oxidative-mediated damage to the lipid components of brain tissue resulting from scopolamine administration. Both blood serum and brain changes in oxidative stress status were observed following 8-day treatments with Ramipril, Losartan, scopolamine, and combinations. While the serum oxidative stress modulation observed in this study could suggest the potential effect of RAAS modulation and scopolamine administration on the circulatory system, blood vessels endothelia, and arterial tension modulation, the observed brain tissues oxidative stress modulation could lead to important information on the complex interaction between renin-angiotensin and cholinergic systems.
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In recent decades, new alternative therapies using drugs containing active ingredients of natural origin have been a hot topic for medical research. Based on the confirmed therapeutic potential of the Vinca minor plant, considered in the specialized literature to be of pharmaceutical interest, the purpose of this study is to determine the chemical and mineral composition of the Vinca minor plant grown in the Dobrogea area, with a view to its use in the formulation of dermal preparations. For this purpose, plant materials were collected from the mentioned area and hydroalcoholic macerates of different concentrations were obtained: 40%, 70% and 96% from leaves (F40, F70, F96) and stems (T40, T70, T96) of Vinca minor plant to determine the optimal extraction solvent. The hydroalcoholic macerates were analyzed via the HPLC method for the identification and quantification of the main bioactive compounds, and two methods were used to evaluate their antioxidant properties: the DPPH radical scavenging test and the photochemiluminescence method. HPLC analysis showed the presence of four indole alkaloids: vincamine, 1,2-dehydroaspidospermidine, vincaminoreine and eburnamonine. Vincamine was the alkaloid found in the highest concentration in Vinca leaves (2.459 ± 0.035 mg/100 g d.w.). The antioxidant activity of Vinca minor hydroalcoholic macerates showed values between 737.626-1123.500 mg GAE/100 g d.w (DPPH test) and 77.439-187.817 mg TE/100 g d.w (photochemiluminescence method). The concentrations of toxic metals Cd, Cu, Ni, Pb in dried leaves and stems of Vinca minor, determined by AAS, were below detection limits.
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Alcaloides , Vinca , Vincamina , Antioxidantes/farmacologia , Antioxidantes/análise , Vinca/química , Alcaloides/análise , Plantas , Minerais/análise , Folhas de Planta/química , Extratos Vegetais/análiseRESUMO
Black poplar buds have high contents of many compounds with therapeutic potential, which are useful in cosmetics and the treatment of various dermatitis, respiratory diseases, etc. The aim of this study was to identify and exploit the local plant resources with biologically active properties from the Dobrogea area, Romania. For this purpose, materials were collected from the mentioned area, and macerates of black poplar were prepared in order to evaluate their qualities as antioxidant and antimicrobial agents. Three different black poplar buds' hydroalcoholic macerates were analyzed by the Folin-Ciocâlteau method to estimate the total content of phenolic compounds, by the HPLC-DAD method for identification and quantification of the main bioactive compounds and by the DPPH radical scavenging method to evaluate the antioxidant activity. All hydroalcoholic macerates showed high concentrations of phenolic compounds, the main individual compounds being gallic acid, chlorogenic acid, cinnamic acid, and methyl gallic acid. The antioxidant activity of the black poplar buds' hydroalcoholic macerates, evaluated by the DPPH radical scavenging test, showed high values, between 496 and 1200 mg GAE /100 g d.w. The Cd, Cu, Zn, Ni, and Pb concentrations released in dry poplar buds, determined by AAS, were below the detection limits. Hydroalcoholic macerates of black poplar were tested against two groups of gram-positive bacteria (Enterococcus and Staphylococcus) using an agar well diffusion assay. The in vitro inhibitory activities of the macerates were important and ranged from 8.2-9.4 mm inhibition zones (Staphylococcus) to 8.6 -10 mm inhibition zones (Enterococcus).
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Anti-Infecciosos , Populus , Antioxidantes/farmacologia , Antioxidantes/química , Populus/química , Antibacterianos/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Anti-Infecciosos/farmacologia , Fenóis/farmacologiaRESUMO
Alarming statistics show that the number of people affected by excessive weight has surpassed 2 billion, representing approximately 30% of the world's population. The aim of this review is to provide a comprehensive overview of one of the most serious public health problems, considering that obesity requires an integrative approach that takes into account its complex etiology, including genetic, environmental, and lifestyle factors. Only an understanding of the connections between the many contributors to obesity and the synergy between treatment interventions can ensure satisfactory outcomes in reducing obesity. Mechanisms such as oxidative stress, chronic inflammation, and dysbiosis play a crucial role in the pathogenesis of obesity and its associated complications. Compounding factors such as the deleterious effects of stress, the novel challenge posed by the obesogenic digital (food) environment, and the stigma associated with obesity should not be overlooked. Preclinical research in animal models has been instrumental in elucidating these mechanisms, and translation into clinical practice has provided promising therapeutic options, including epigenetic approaches, pharmacotherapy, and bariatric surgery. However, more studies are necessary to discover new compounds that target key metabolic pathways, innovative ways to deliver the drugs, the optimal combinations of lifestyle interventions with allopathic treatments, and, last but not least, emerging biological markers for effective monitoring. With each passing day, the obesity crisis tightens its grip, threatening not only individual lives but also burdening healthcare systems and societies at large. It is high time we took action as we confront the urgent imperative to address this escalating global health challenge head-on.
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Cirurgia Bariátrica , Obesidade , Animais , Obesidade/complicações , Obesidade/terapia , Obesidade/epidemiologiaRESUMO
The conundrum of Cannabis sativa's applications for therapeutical purposes is set apart by the hundreds of known and commercially available strains, the social, cultural and historical context, and the legalization of its use for medical purposes in various jurisdictions around the globe. In an era where targeted therapies are continuously being developed and have become the norm, it is imperative to conduct standardized, controlled studies on strains currently cultivated under Good Manufacturing Practices (GMP) certification, a standard that guarantees the quality requirements for modern medical and therapeutic use. Thus, the aim of our study is to evaluate the acute toxicity of a 15.6% THC: <1% CBD, EU-GMP certified, Cannabis sativa L. in rodents, following the OECD acute oral toxicity guidelines, and to provide an overview of its pharmacokinetic profile. Groups of healthy female Sprague-Dawley rats were treated orally with a stepwise incremental dose, each step using three animals. The absence or presence of plant-induced mortality in rats dosed at one step determined the next step. For the EU GMP-certified Cannabis sativa L. investigated, we determined an oral LD50 value of over 5000 mg/kg in rats and a human equivalent oral dose of ≈806.45 mg/kg. Additionally, no significant clinical signs of toxicity or gross pathological findings were observed. According to our data, the toxicology, safety and pharmacokinetic profile of the tested EU-GMP-certified Cannabis sativa L. support further investigations through efficacy and chronic toxicity studies in preparation for potential future clinical applications and especially for the treatment of chronic pain.
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Cryptorchidism, defined as the failure of at least one or both testicles to descend into the scrotal pouches, is the most frequent (1.6-9% at birth, 1/20 males at birth) congenital anomaly encountered in newborn males, resulting in one of the most frequent causes of non-obstructive azoospermia in men. Similar to other congenital malformations, cryptorchidism is thought to be caused by endocrine and genetic factors, combined with maternal and environmental influences. The etiology of cryptorchidism is unknown, as it involves complex mechanisms aiming to control the testicular development and descent from their initial intra-abdominal location in scrotal pouches. The implication of insulin-like 3 (INSL-3) associated with its receptor (LGR8) is critical. Genetic analysis discloses functionally deleterious mutations in INSL3 and GREAT/LGR8 genes. In this literature review, we discuss and analyze the implication of INSL3 and the INSL3/LGR8 mutation in the occurrence of cryptorchidism in both human and animal models.
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Cardiorenal syndrome (CRS) denotes the bidirectional interaction of chronic kidney disease and heart failure with an adverse prognosis but with a limited understanding of its pathogenesis. This study correlates biochemical blood markers, histopathological and immunohistochemistry features, and 2-deoxy-2-fluoro-D-glucose positron emission tomography (18F-FDG PET) metabolic data in low-dose doxorubicin-induced heart failure, cardiorenal syndrome, and renocardiac syndrome induced on Wistar male rats. To our knowledge, this is the first study that investigates the underlying mechanisms for CRS progression in rats using 18F-FDG PET. Clinical, metabolic cage monitoring, biochemistry, histopathology, and immunohistochemistry combined with PET/MRI (magnetic resonance imaging) data acquisition at distinct points in the disease progression were employed for this study in order to elucidate the available evidence of organ crosstalk between the heart and kidneys. In our CRS model, we found that chronic treatment with low-dose doxorubicin followed by acute 5/6 nephrectomy incurred the highest mortality among the study groups, while the model for renocardiac syndrome resulted in moderate-to-high mortality. 18F-FDG PET imaging evidenced the doxorubicin cardiotoxicity with vascular alterations, normal kidney development damage, and impaired function. Given the fact that standard clinical markers were insensitive to early renal injury, we believe that the decreasing values of the 18F-FDG PET-derived renal marker across the groups and, compared with their age-matched controls, along with the uniform distribution seen in healthy developing rats, could have a potential diagnostic and prognostic yield in cardiorenal syndrome.
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Síndrome Cardiorrenal , Insuficiência Cardíaca , Animais , Masculino , Ratos , Síndrome Cardiorrenal/diagnóstico por imagem , Ratos Wistar , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , DoxorrubicinaRESUMO
In recent years, many healthcare systems, along with healthcare professionals, have provided services in a patient-centered manner, in which patients are key actors in the care process. Encouraging self-care creates responsible patients, but it must be practiced responsibly. This study aims to analyze the tendency towards self-medication for patients from a rural area in Northeastern Romania. Data were collected using a questionnaire, which consisted of 25 questions, that has been developed by the research team. Student's T test or one-way ANOVA was used, and the reliability of the questionnaire was calculated using Cronbach's alpha coefficient. Fifty-eight patients agreed to participate and were interviewed. The results of the study suggest that respondents practice self-medication, which they resort to when their condition cannot be treated with natural remedies or herbs and when it impairs their ability to do their daily activities. Self-medication could be explained by the lack of self-care services as well as the trust patients have in the specific treatment. Patients prefer asking the pharmacist for drugs instead of visiting a physician, which could be due to higher accessibility and time-efficiency, while also being prone to stock up on certain medications due to limited access to healthcare.
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Hábitos , Automedicação , Humanos , Romênia , Reprodutibilidade dos Testes , FarmacêuticosRESUMO
Chronic neuropathic pain (CNP) affects around 10% of the general population and has a significant social, emotional, and economic impact. Current diagnosis techniques rely mainly on patient-reported outcomes and symptoms, which leads to significant diagnostic heterogeneity and subsequent challenges in management and assessment of outcomes. As such, it is necessary to review the approach to a pathology that occurs so frequently, with such burdensome and complex implications. Recent research has shown that imaging methods can detect subtle neuroplastic changes in the central and peripheral nervous system, which can be correlated with neuropathic symptoms and may serve as potential markers. The aim of this paper is to review available imaging methods used for diagnosing and assessing therapeutic efficacy in CNP for both the preclinical and clinical setting. Of course, further research is required to standardize and improve detection accuracy, but available data indicate that imaging is a valuable tool that can impact the management of CNP.
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Neuralgia , Humanos , Neuralgia/diagnóstico por imagem , Neuralgia/terapia , Sistema Nervoso Periférico , Biomarcadores , Diagnóstico por ImagemRESUMO
The endocannabinoid system (ECS) dynamically regulates many aspects of mammalian physiology. ECS has gained substantial interest since growing evidence suggests that it also plays a major role in several pathophysiological conditions due to its ability to modulate various underlying mechanisms. Furthermore, cannabinoids, as components of the cannabinoid system (CS), have proven beneficial effects such as anti-inflammatory, immunomodulatory, neuromodulatory, antioxidative, and cardioprotective effects. In this comprehensive review, we aimed to describe the complex interaction between CS and most common age-related diseases such as neuro-degenerative, oncological, skeletal, and cardiovascular disorders, together with the potential of various cannabinoids to ameliorate the progression of these disorders. Since chronic inflammation is postulated as the pillar of all the above-mentioned medical conditions, we also discuss in this paper the potential of CS to ameliorate aging-associated immune system dysregulation.