Abstract in English:

Abstract The Corneometer CM® 825 from Courage & Khazaka electronic GmbH is widely utilized in clinical efficacy testing of cosmetics. Assessing methodological variables is crucial for ensuring the reliability of the process. The aim of this study was to evaluate the operational and instrumental parameters of the Corneometer CM® 825 in the clinical assessment of skin hydration levels. Precision and accuracy of the measurements were assessed by measuring hydration levels on 10 participants in specific areas of the forearm and face. Three different skin conditions (dry, normal, and hydrated) resulting from the use or non-use of moisturizing cosmetics and a drying promoter were evaluated within 120 minutes of their application. The electrical capacitance method demonstrated good repeatability, with coefficients of variation mostly below 10%. However, higher variability was observed in inter-observer readings. The equipment exhibited high sensitivity and accurately discriminated the differences between hydrated and dry skin. Operational training and standardization of the methodology are essential to ensure accurate, reproducible, and reliable results in studies utilizing the Corneometer equipment for assessing skin hydration levels.

Abstract in English:

Abstract L-theanine has neuromodulatory properties, such as attenuate anxiety disorders and stress. Stress is a situation characterized by the stimulus to cortisol secretion and without specific pharmacological therapies. Thus, this study investigates the effect of L-theanine on the response to acute stress, evaluated by tissue cortisol level, oxidative status markers, and behavioral parameters, in zebrafish. The animals were divided into six groups: G1: control, G2: treated with L-theanine 45 mg/L, G3: treated with L-theanine 100 mg/L, G4: stress, G5: stress+L-theanine 45 mg/L and G6: stress+L-theanine 100 mg/L. Before the execution of the acute stress protocol that consisted of chasing the animals with a net for two minutes, exposure to L-theanine was performed in aquarium water for 1 hour. Tissue cortisol levels were analyzed, as well as cerebral oxidative status (lipoperoxidation and levels of thiolic compounds) and fish behavior (new tank test). L-theanine at a concentration of 45 mg/mL modulated the effects of acute stress on zebrafish, inhibiting increased levels of tissue cortisol. However, it was not able to alter the behavior or oxidative status of the animals. Thus, we conclude that the administration of L-theanine can promote acute stress attenuation, modulating the pathological responses of stress.

Abstract in English:

Abstract Drug addiction is one of the most important global problems. Medicinal herbs have been traditionally used in the management and treatment of opioid withdrawal syndrome and pain. The aim of this study was to determine the effect of A. dracunculus essential oil in reducing the symptoms of morphine withdrawal in mice. Male mice (25-30 g) were randomly assigned into 4 groups (n=10). Morphine-dependent groups received morphine (50 and 75 mg/kg ip; three times/day, 3 days) and a single injection of morphine (50 mg/kg) and then naloxone on the fourth day via IP injection. The control group received saline. The post-treated group received morphine for 3 days; on the fourth day, ten minutes before receiving naloxone, A. dracunculus essential oil with a dose of 75 mg/kg was injected. All groups received naloxone 2 hours after receiving the last dose of morphine; then, the morphine withdrawal symptoms were measured for 30 minutes. In the post-treated and co-treated groups, the body stretching and shaking the claw were significantly less than morphine-dependent groups (p<0/05). Also, in the post-treated and co-treated groups, the blinking, itching, and the number of standing on two legs significantly decreased compared to the morphine group. Hence, it might be concluded that A. dracunculus essential oil can significantly reduce morphine withdrawal symptoms.

Abstract in English:

Abstract The aim of the present study is to develop a chitosan based herbal formulation using rhubarb for wound healing. Wound healing is a dynamic process facilitating the regeneration or repair of broken tissue. Rhubarb is commonly used worldwide for their effective antiseptic, antifungal and antiviral properties. Rhubarb loaded chitosan nanoparticles were prepared by ionic cross-linking process with sodium lauryl sulphate. The optimized formulation was examined for antibacterial activity against S. aureus and P. aeruginosa. Wound healing effects of the developed formulation was studied on excision wound model in Wistar albino rats. Average particle size and zeta potential of chitosan nanoparticles varied from 93 to 2,225 nm and from+30.82 to -16.08 mV, respectively. On the basis of particle size, zeta potential, and % entrapment, Formulation C 4 (0.0595% chitosan, 0.535% cross-linker, and 1% drug) was selected among different checkpoint formulation and further studies were performed. Hydrogel was developed using a combination of polyvinylpyrrolidone and carboxymethyl cellulose. Nanoformulation based hydrogel showed significantly enhanced antimicrobial activity against tested pathogenic microbial strains in comparison to drug solution, as well as marketed formulations.

Abstract in English:

Abstract Entecavir is an inhibitor of hepatitis B virus (HBV) DNA synthesis that has been widely prescribed in the treatment of chronic infections caused by the virus. Production of generic ETV drugs is an ongoing global endeavor, with particular significance for developing countries that rely on importing the expensive reference drug. ETV-excipient compatibility studies were conducted with the declared inputs in solid pharmaceutical formulations on the market through thermal analysis and HPLC techniques. Thermal analyses by TGA and DTA indicated compatibility of entecavir with the excipients microcrystalline cellulose, crospovidone, titanium dioxide, magnesium stearate, hypromellose, polyethylene glycol and povidone; this was confirmed via HPLC. Lactose monohydrate proved to be incompatible with ETV in thermal and chromatographic assays. The thermal analysis of marketed solid dosage forms revealed a predominance of the lactose monohydrate profile at the expense of ETV and other inputs in the TGA and DTA curves, due to its high content in the formulations; this makes the evidence of ETV-lactose chemical interaction even more important. Compatibility tests by HPLC showed no chemical interaction of ETV with the excipient mannitol, a soluble diluent proposed as a replacement for lactose monohydrate, with the same function in the formulation.

Abstract in English:

Abstract In this work, a methodology was developed to obtain dietary fiber from agro-industrial fruit and vegetable waste. The resulting raw material was named DF. The physicochemical analysis revealed a high total dietary fiber content, along with an appropriate soluble to insoluble fiber ratio and excellent water and fat retention capacity. Subsequently, its potential protective effect against hepatotoxicity induced by valproic acid (VPA) was investigated in Wistar rats, both as preventive and curative treatments. For this purpose, two different trials were conducted. In the preventive trial, VPA (250 mg/kg/day; oral) was administered concomitantly with DF (0.3 and 0.15 mg/kg/day) for 14 days. In the curative trial, VPA was administered for 14 days, followed by DF for an additional 14 days. The results demonstrated that DF supplementation normalized body weight, liver biomarkers and attenuated VPA-induced tissue damage, while normal liver architecture was preserved. These findings suggest that DF obtained from agro-industrial fruit and vegetable waste materials may serve as a functional feedstock to counteract the harmful effects associated with prolonged VPA treatment.

Abstract in English:

Abstract The level of understanding about disease and treatment is an important factor to consider in achieving favorable outcomes in patients with mental disorders, and adherence to pharmacological treatment is crucial in this regard. The aim of this study was to assess to what extent patients with MD undergoing an integrated pharmaceutical care model with telepharmacy showed improvements in factors related to treatment adherence and their level of knowledge about pharmacotherapy. A parallel randomized clinical trial was conducted with a two-arm study in two Psychosocial Care Centers located in a state capital in Brazil. Participants in the intervention group received a comprehensive pharmaceutical care model that included attitudinal, technical, and educational interventions, while the control group received standard routine care. Predictive factors for adherence to pharmacological treatment and level of medication knowledge were assessed before and after the intervention. In the intervention group (33), significant improvements were found in the scores of adherence predictors (p<0.001) and the level of knowledge of pharmacotherapy (p<0.001) from baseline to follow-up, compared to the control group (33). The telepharmacy model demonstrated effectiveness in enhancing the scores of adherence predictors for pharmacological treatment and improving the level of knowledge of pharmacotherapy among patients with mental disorders.

Abstract in English:

Abstract Belonging to the Alismataceae family, Echinodorus macrophyllus, known in Brazil as “chapéu de couro”, is popular in the food industry, where it is used in teas and infusions. The objective of this study was to evaluate the active chemical compounds in the powder of E. macrophyllus leaves extracted by two different methods (Soxhlet [SXT] and ultrasound-assisted extraction [UAE]), quantify the total phenolic compound (TPC) and total flavonoid (TFC) content, and evaluate the antioxidant potential and larvicidal activity. The SXT extraction was the most efficient (6.05% yield). Analysis by thin-layer chromatography (TLC) and high-performance liquid chromatography with a diode array detector (HPLC-DAD) evidenced the presence of cinnamic acid derivatives, flavones, and flavanones in the extracts. The TPC was higher in the SXT extract (7.71±0.05 µg GAE/mL). However, there was no significant difference in TFC. The SXT extract exhibited greater antioxidant potential according to the ferric reducing antioxidant power (FRAP) method (IC50=3.37±0.45 µg/mL), while the UAE extract showed higher activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) (IC50=42.16±5.79 µg/mL). Both extracts were nontoxic to Artemia salina, suggesting the potential health benefits of this plant, which is rich in phenolic compounds and diverse pharmacological properties.

Abstract in English:

Abstract Hybrid structures containing multiple pharmacophore units with known activity have attracted attention due to their promising outcomes. In this study, several new hybrid structures containing benzimidazole and thiadiazole units were synthesized. The newly synthesized compounds were structurally analyzed using 1H-NMR, 13C-NMR, HRMS, and elemental analysis. The antimicrobial, in vitro anti-cancer, and antioxidant activities of all compounds were investigated. In vitro antimicrobial activities of the compounds were determined against Gram-positive (S. aureus ATCC 29213, E. faecalis ATCC 29212), Gram-negative (E. coli ATCC 25922, P. aeruginosa ATCC 27853) bacteria and fungi (C. albicans ATCC 10231) by using broth microdilution method. The compound 5g bearing 4-methoxyphenyl derivative showed the best activity with 32 μg/mL against S. aureus ATCC 29213 and P. aeruginosa ATCC 27853. The MTT test was used to determine the cytotoxicity of the produced compounds on the MCF-7 (human breast cancer) and L-929 (fibroblast) cell lines. FRAP method was used to determine the antioxidant properties of synthesized compounds. The Ferric Reducing Antioxidant Power of the compounds 5a, 5b, and 5c showed more antioxidant properties than vitamin E. The compound 5g stands out in the series in that it is not toxic on the healthy cell line and has promising antimicrobial activity.

Abstract in English:

Abstract Mikania glomerata (guaco) is included in Brazil’s National List of Essential Drugs (RENAME) with expectorant and bronchodilator indications. This research aims to describe the profile of patients and prescribers of guaco-based herbal medicines within the Unified Health System in the municipalities of Rio Grande do Sul (RS)/Brazil, quantify the consumption and cost of this product, and assess the prescriber’s experience with guaco and herbal medicine. A cross-sectional observational study was conducted based on questionnaires applied to prescribers and guaco usage data in primary care in RS municipalities (May 1, 2020 - April 30, 2021). 44 municipalities (40%) were identified dispensing guaco syrup in the sample. The results showed a prevalence of women users (57.4%) and patients between 19 and 59 years of age (58.2%). All participating prescribers were physicians, and 37% of the responses indicated daily doses of coumarin lower than recommended. The syrup consumption per 1,000 inhabitants ranged from 0.3 to 36.6 bottles, and the monthly cost per municipality varied from $0.50 to $247.78. Only five prescribers (21.7%) were familiar with the herbal medicines in RENAME, and only one had formal training for prescribing herbal medicines, highlighting the need for instruction and dissemination of programs for using herbal medicines.

Abstract in English:

Abstract Collagen, the predominant protein in various organisms, is pivotal for tissue structure and mechanical properties. It has been extensively studied for its cosmetic, surgical, and anti-ageing applications, reflecting a growing interest in collagen-based cosmetics in Romania and prompting further research in this area. The study aimed to assess collagen’s efficacy and safety in dermocosmetology, comparing collagen peptides’ effectiveness in oral and topical applications. An analysis of the published studies on the subject was carried out, comparing the effectiveness of using collagen in different ways to improve skin conditions. The investigation included a literature review on collagen’s role in enhancing skin properties, covering its discovery, structure, chemical composition, systemic and topical applications, diverse sources, and skin penetration mechanisms. Hydrolysed collagen and its antioxidant properties are considered. The methods of investigating and monitoring the safety of cosmetic preparations are described. It has been concluded that topical collagen, similarly to nutraceutical supplements with collagen peptides, can slow down and reduce the signs of skin ageing and can increase skin elasticity, density, and moisture in equal measure. Studies have confirmed the harmlessness of collagen beyond doubt, but further investigation is necessary to determine the effectiveness of using different types of collagen.

Abstract in English:

Abstract The transdermal pathway serves as a significant route for achieving localized or systemic effects. Within this context, the stratum corneum is a crucial barrier limiting the permeation of many drugs. To surmount this barrier, carriers, and nanocarriers have been utilised, notably ‘invasome’ being one such example. In our study, we formulated invasomes loaded with simvastatin using the conventional thin-layer evaporation technique. This formulation involved the use of soy phosphatidylcholine, terpene (Limonene), chloroform, and ethanol. Simvastatin-loadedinvasomes were incorporated into a carbopol 934 solution to create a gel. We prepared and assessed different formulationsfor various parameters, including zeta potential, scanning electron microscopy, entrapment efficiency, viscosity, and drug content, and conducted in vitro studies. The entrapment efficiency was as high as 83.17±0.61%. The maximum in vitro drug permeation (45.44±0.4%) was found in the gel with 0.5% soy phosphatidylcholine and 0.25% terpene. Upon evaluating these parameters, our findings suggest that the simvastatin invasomal gel effectively enhances drug permeability across membranes and successfully achieves prolonged drug release.

Abstract in English:

Abstract Caused by the protozoan Trypanosoma cruzi, Chagas disease affects six to seven million people worldwide, mainly in Latin America. The drugs currently available for treating the disease are ineffective during its chronic phase and have serious adverse effects. Essential for the survival of T. cruzi, the enzyme dihydroorotate dehydrogenase (DHODH) has become a key molecular target for drug discovery in Chagas disease. This study investigates the bi-dimensional and three-dimensional quantitative structure-activity relationships (QSAR) for a series of 64 T. cruzi DHODH inhibitors. The results indicate a highly predictive 2D Hologram QSAR (HQSAR) model (q 2 = 0.65, r 2 = 0.88, and r 2 pred = 0.82) that identified key molecular fragments that correlate with DHODH inhibition. Moreover, 3D Comparative Molecular Field Analysis (CoMFA) models (q 2 = 0.75, r 2 = 0.99, and r 2 pred = 0.66) pointed out the 3D molecular features that determine the activity of the inhibitors. Although restricted to a congeneric series and focused solely on 2D and 3D descriptors, these QSAR models and molecular docking analyses identified key properties and intermolecular interactions for designing and optimizing new compounds as potent T. cruzi DHODH inhibitors.

Abstract in English:

Abstract The study aimed to assess the prevalence and characteristics of potential drug-drug interactions (pDDIs) that increase the risk of QT prolongation, in a population of cardiovascular disease patients. An observational retrospective study was conducted at a cardiology ward. A total of 351 patients were included in the analysis, with almost equal gender distribution (female 48.4%) and mean age 70±10 years. In the total set of tested drug pairs (5620), QT-prolonging pDDIs were identified in 13 drug pairs on admission. The highest frequency was observed for ciprofloxacin (involved in 5 pDDIs), followed by propafenone (4 pDDIs) and beta2-agonists (4 pDDIs). The pharmacodynamic mechanism was involved in all pDDIs. The study revealed a low prevalence of QT-prolonging pDDIs on admission to the cardiology ward, about 3% in the studied population. However, given that underlying heart disease is a significant risk factor for the occurrence of QTc prolongation, the additional risk for acquired QT prolongation should not be neglected. Due to serious consequences caused by QT prolongation and TdP, the key role of health professionals is to identify predisposed patients and to recognize pDDIs involving QT-prolonging agents. Hence, patients’ modifiable risk factors for QT prolongation should be minimized, if not eliminated.

Abstract in English:

Abstract Tagetes minuta L. is a naturalized species that is not endemic to the high-altitude fields of Santa Catarina in southern Brazil. In this study, we investigated the composition of the essential oil (EO) from the flowers of the plant and its larvicidal activity against Aedes aegypti. The EO was obtained by hydrodistillation using a Clevenger apparatus. The chemical composition was determined using gas chromatography coupled with mass spectrometry (GC-MS). The EO extraction yield was 4.9%, and the major compounds (Z)-tagetone, (Z)-β-ocimene, and dihydrotagetone were identified. The 24 h larvicidal activity was verified against that of L3 larvae of the Rockefeller strain of Ae. Aegypti. The EO showed larvicidal activity against Ae. aegypti, with LC50 = 17.28 μg/mL-1. The results indicate that the bioinsecticidal potential of T. minuta EO is promising for the development of research in the field of natural products.

Abstract in English:

Abstract Depression has substantially increased in the last 10 years in Brazil, and mental health became a concerning issue for the public health globally, especially considering the COVID-19 pandemic. The therapeutic conduct in depression mainly relies on medication and psychotherapy. However, more than one attempt in the treatment can be considered a common procedure before finding out the right medication. This conduct leads many patients to give up following pharmacological treatment. In this scenario, pharmacogenomics emerges as a possible supporting tool of the medical treatment. This paper aims to analyze the scenario of depression in Brazil and the viability of pharmacogenomic tests implementation as a part of the medical procedure. Official data bank from the Brazilian government was used to analyze the prevalence of depressive disorder, as well as Pharmacogenomic data bases and relevant articles around this topic. Additionally, pharmacogenomic tests typically take into consideration the genes CYP2D6 and CYP2C19, which are relevant for antidepressant treatment. Data shows that these tests could help patients achieve remission of symptoms, and they could also be economically advantageous. Thus, pharmacogenomic tests present as an interesting approach for the therapeutic conduct of depression and can significantly improve the health quality of this affected population.

Abstract in English:

Abstract Healthcare during the COVID-19 pandemic may have led to the inappropriate use of antimicrobial agents and contributed to elevated multidrug resistance. The aim of this study was to analyze the consumption of antibacterial agents at a hospital complex from 2018 to 2021. Drug utilization study using antibacterial agents consumption data. The groups of antibacterial agents most consumed in the hospital complex were carbapenems, penicillins + beta-lactamase inhibitors, beta-lactamase-resistant penicillins, glycopeptides, and fluoroquinolones. The drugs with a compound annual growth rate that increased by more than 20% from 2018 to 2021 were amikacin (50.12%), benzylpenicillin (24.33%), oral clarithromycin (51.06%), daptomycin (34.38%), polymyxin B (20.85%), and tigecycline (41.49%). According to the AWaRE classification, the antibacterial agents from the Watch group subjected to AWaRE exhibited increased consumption in all years of the study. On the other hand, there was a reduction in the access category. In turn, the consumption of antibacterial agents in the reserve category also increased. The pattern of antimicrobial consumption in the hospital complex showed increased consumption in medical clinics and intensive care units, with a predominance of carbapenems, penicillins + beta-lactamase inhibitors, beta-lactamase-resistant penicillins, glycopeptides, fluoroquinolones, and polymyxin B, reflecting the care profile and influence of the COVID-19 pandemic.

Abstract in English:

Abstract The study investigates the potential of Morus alba L. (mulberry) young and ripe fruit extracts against lung cancer cells. Cancer ranking as the second leading cause of global mortality, it is essential to investigate natural compounds like phytochemicals for therapeutic benefits. The research investigates presence of phytochemicals and antioxidant activity of both young (MAF-Y) and ripe (MAF-R) mulberry fruit extracts. Results revealed presence of various secondary metabolites, particularly high phenolic content and antioxidant properties in MAF-R. Both extracts demonstrated significant cytotoxicity against lung adenocarcinoma cells (A549), with IC50 18.4 ± 3.01µg/ml (MAF-R) and 29.41 ±3.6 µg/ml (MAF-Y). Moreover, the extracts effectively inhibited cell migration. Treatment of extracts elevated reactive oxygen species (ROS) production which resulted in disruption of mitochondrial membrane potential, and induced the process of apoptosis in lung carcinoma cells. This was evidenced through various assays including differential staining and DNA fragmentation analysis. These findings underscore the potential of mulberry fruit extracts as promising candidates for cancer prevention and treatment due to their antioxidant properties, cytotoxic effects, and ability to induce apoptosis in lung cancer cells.

Abstract in English:

Abstract Antimicrobial drug resistance is a challenge to public health. Various microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, carbapenemase-producing Klebsiella pneumoniae, Pythium insidiosum, and Candida auris, have developed resistance to commonly used antimicrobials in infection disease treatments. Consequently, there is an urgent need to explore and develop novel therapeutic drugs. Natural products, particularly medicinal plants, have received attention in the quest for innovative treatments for various diseases. Plantago major is a plant endowed with several biological properties, such as antibacterial, antifungal, and healing actions. This study aimed to investigate the antimicrobial activities of the methanolic extract obtained from the leaves of P. major. Microdilution assays were conducted to determine the minimum inhibitory concentration and minimum bactericidal and fungicidal concentration. Additionally, synergism with antimicrobial drugs was assessed using a time-kill curve analysis. A synergistic bactericidal interaction between the extract and imipenem was observed against carbapenemase-producing K. pneumoniae. For MRSA, a bacteriostatic synergism was noted in combinations of the extract with cephalotin and oxacillin. For C. auris, a fungistatic interaction was observed between the extract and amphotericin B. These results suggest the presence of bioactive compounds within the extract with therapeutic potential for combating infections caused by these microorganisms.

Abstract in English:

Abstract Metformin hydrochloride (MTF) has pharmacological properties for managing inflammatory skin conditions. MTF is a hydrophilic medication. Accordingly, embedding MTF into lipid carriers for enhancing skin penetration presents a challenge. The study aims to optimize the loading of MTF into nanostructured lipid carriers (NLCs) using a 22 full factorial design, employing the solvent injection technique. The NLCs were evaluated for encapsulation efficiency, hydrodynamic diameter, zeta potential, and polydispersity index. Alkalinization of the aqueous phase (pH = 12.5) resulted in maximizing the entrapment of MTF within NLCs. Furthermore, the tested solid lipids impacted the encapsulation of MTF based on their hydrophilic-lipophilic balance. The optimized formulation is composed of a lipid phase incorporating beeswax (75 mg), oleic acid (25 mg), and Span 60 (1% w/w), and an aqueous phase comprised of 1% w/w Tween 80, pH 12.5. The selected formula attained an entrapment efficiency of 53.68 ± 0.27%, a particle size of 333.0 ± 6.4 nm, and a negative surface charge, indicating adequate particles` stability. DSC and Molecular docking analyses confirmed the MTF incorporation within the lipid phase. The outcomes emphasize the importance of optimizing investigations in developing a viable delivery system for MTF to boost its permeation across the skin layers.

Abstract in English:

Abstract Traditionally, raw cow milk has been employed to treat acid and thermal burns due to its antibacterial, antibiotic, and antifungal properties. It also aids in preventing scarring and alleviating burn-related skin discomfort. This study focuses on evaluating a nanoemulsion cream made from casein extracted from raw cow milk for managing acid and thermal burns. Casein was isolated and used to create 2%, 5%, and 10% w/w nanoemulsion creams. Wistar albino rats were used to induce acid and thermal burns, and the healing progress was monitored by measuring wound contraction and epithelialization period. The results demonstrated significant wound healing effects of the casein creams (p<0.001) in acid burns, with the 10% w/w cream showing the highest epithelization rate in thermal burns. Raw milk also exhibited notable healing properties in acid burns. However, its effectiveness was relatively lower in thermal burns. This study suggests that raw milk and its casein-derived creams could be utilized as first-aid treatments for acid burns, though they may be less effective for thermal burns.

Abstract in English:

Abstract The juice of blood oranges, especially those of the Citrus sinensis variety Moro, cultivated in the region of Sicily (Italy), is an increasingly popular drink due to its beneficial health properties, such as its ability to reduce abdominal fat, related to its anthocyanin constituents, especially cyanidin-3-O-glycoside (C3G), as demonstrated in pre-clinical and clinical studies. However, the dry extract of C. sinensis juice currently available at compounding pharmacies in Brazil includes samples from various countries, some of which may not have adequate climatic conditions for the production of anthocyanins. In this work, we investigated samples from the three major suppliers (reference, A1, and A2). The composition of the samples was analyzed by LC-UV and LC-MS, total anthocyanin content (TAC), antioxidant activity (DPPH assay), and in vitro anti-inflammatory effect, by NO production in macrophages. C3G was detected only in the reference sample (1.6%), the TAC values were 1.45%, 0.1% and 0.01% in the reference, A1, and A2, respectively. The reference and A1 showed similar antioxidant activity (EC50 of 45.6 and 62.4 µg/mL, respectively), while A2 showed lower activity (EC50 315.1 µg/mL). Only the reference sample showed significant inhibition of NO release, demonstrating the need for quality control of these commercialized samples.

Abstract in English:

Abstract This research aims to create dabrafenib (DBF)-loaded nanosponges (NSPs) using β-cyclodextrin (β-CD) and diphenyl carbonate (DPC) as linker to improve oral bioavailability. DBF-loaded β-CD NSPs were synthesized by finely adjusting the molar ratio of β-CD to DPC and optimizing the stirring rate and duration using design methodology. After being loaded with DBF, the produced β-CD NSPs were characterized in terms of particle size, zeta potential (Z.P), polydispersity index (PdI), and drug entrapment efficiency (E.E). Studies on compatibility were carried out with FTIR (Fourier Transform Infrared Spectroscopy) and DSC (Differential Scanning Calorimetry). Permeability, in vivo, and in vitro experiments were performed on the improved NSPs and the pure medication. After optimizing DBF-loaded β-CD NSPs, a formulation with a mean size of 158.0 ± 7.2 nm, PdI of 0.282 ± 0.0044, and E.E of 86.23 ± 2.45% was obtained, based on the assessments indicated earlier. Zeta sizer, SEM, spectrum analysis, in vitro release, and pharmacokinetic tests were among the other analyses that further validated the optimization. An area under the curve (AUC0-t) of 7.95-fold greater and a Cmax 7.356 times higher than those of the free drug was demonstrated by the optimized β-CD NSPs, which showed a notable boost. The use of DBF-loaded NSPs holds promise as an effective strategy for enhancing release and bioavailability in the treatment of melanoma.

Abstract in English:

Abstract Epilepsy affects around 50 million people worldwide, with 30% of them being refractory epilepsy. This shows that there is still a need for novel anti-seizure medication that have different mechanisms. One of the most common types of refractory epilepsy is temporal lobe epilepsy. Among the several effects of seizures on neurons is an increase in intracellular Ca2+ and activation of RhoA. Rapamycin is mTORC1 inhibitor, but long-term exposure to rapamycin (>18 hours) could also inhibit mTORC2. RhoA signaling pathway is regulated through the mTORC2 pathway; thus we hypothesized that long-term exposure to rapamycin could inhibit intracellular Ca2+ and RhoA activity as one of the mTORC2 downstream proteins, in a temporal lobe epilepsy model. This study used organotypic hippocampal slice cultures (OHSC) which were exposed to 20 nM rapamycin treatment for 3, 5, 8, and 10 days after induction of epilepsy by 7 μM kainic acid administration for 48 hours. Intracellular calcium concentration was observed using CLSM and RhoA activity with western blot. The results obtained from this research were long-term administration of rapamycin can decrease intracellular calcium concentration and RhoA activity in OHSC models of epilepsy induced by kainic acid, with the most effective duration is 5 days of exposure to rapamycin.

Abstract in English:

Abstract Skin oxidation can impair physiological functions and induce skin diseases, such as photoaging and cancer. L-ascorbic acid (L-AA), or vitamin C, is commonly used in cosmetics because it is a potent antioxidant, inhibits melanogenesis, and promotes collagen and elastin synthesis in the skin. This study developed strategies to improve the stability of L-AA in its pure form with or without caffeic acid (CA) and evaluated its clinical efficacy using an ex vivo method. Oil/water emulsions were prepared with antioxidants and normal stability tests were conducted (various temperatures for 360 days). Antioxidant activity was assessed using a DPPH assay, and L-AA content was quantified by high-performance liquid chromatography. The thiobarbituric acid reactive substances method characterized the inhibition of lipid peroxides in the stratum corneum ex vivo. The formulation F1 (base + 10.0% L-AA) exhibited better L-AA stability over 360 days. The formulations F1 and F2 (base + 10.0% L-AA + 0.2% CA) increased the production of lipid peroxides when applied to the stratum corneum ex vivo and irradiated; however, when not irradiated, they inhibited the production of reactive oxygen species. For greater clinical efficacy of vitamin C on the skin, nighttime use is suggested as well as storage at low temperatures.

Abstract in English:

Abstract Hydroxychloroquine (HCQ) is a chiral drug used to treat malaria and inflammatory diseases, available as a racemic mixture of R-and S-HCQ. This work aimed to build physiologically-based pharmacokinetic (PBPK) models to predict the pharmacokinetics (PK) of R-and S-HCQ and assess the impact of major genetic polymorphisms on PK. Whole-body PBPK models accounting for first-order absorption, Rodgers and Rowland distribution method, and enzyme kinetics data were built for R-and S-HCQ. The models were verified by comparing predicted PK parameters with observed ones, with a mean error within the acceptable range (0.5-2 fold). Simulations covered CYP2D6 normal metabolizer (NM), poor metabolizer (PM), and ultra-rapid metabolizer (UM) phenotypes, as well as CYP2C8 NM and PM phenotypes. The results revealed a 1.1-fold increase in area under the curve blood concentration versus time (AUC) for CYP2D6 PM individuals and a 0.9-fold reduction for UM individuals compared to NM individuals. In addition, simulations with CYP2D6 and CYP2C8 PM phenotype individuals combined with the CYP3A4 inhibitor clarithromycin showed increased AUC for R-and S-HCQ of 2.34 and 2.68, respectively. These PBPK models offer reliable predictions for R-and S-HCQ enantioselective kinetics and shed light on previously unexplored scenarios.

Abstract in English:

Abstract The Covid-19 pandemic, caused by SARS-CoV-2, was responsible for millions of deaths worldwide. The main protease (Mpro) of SARS-CoV-2 is considered one of the important drug targets for the treatment of Covid-19. Recent studies have shown that anisotine should be a potent Mpro inhibitor. In the present work, four oxoquinoline derivatives are proposed as candidates for Mpro inhibitors. The main functional group of these derivatives shows similarity to anisotine, and they are active against the HSV-1, as well as the latter. Molecular docking studies evaluated whether these compounds could be active against Mpro of SARS-CoV-2. Structural modifications were proposed on the oxoquinoline derivative which formed a more stable complex with Mpro and this proposal formed an even more stable complex besides exhibiting improvements in the toxicological profile. Molecular dynamics simulations indicated that derivatives proposed promote greater stabilization by complexing with Mpro than anisotine.

Abstract in English:

Abstract Melatonin straddles the boundary between food supplements and medicine. In Portugal, its classification is contingent upon a critical dosage threshold of 2 mg. This study aimed to detail the composition of melatonin-containing food supplements, available in Portugal based on their labels, and report the number of potential intoxications. Data was collected from 44 food supplements, and the difference in active ingredients was revealed towards the 16 approved medicines. Data on melatonin intoxication cases from 2018 to 2022 were obtained from the Portuguese Poisons Information Center (CIAV). Melatonin supplements, available in tablets, capsules, gummies, powders, or sprays, exhibited a recommended daily dose ranging from 1 to 1.95 mg. Only 20% contained melatonin alone, while the majority included plant extracts and vitamins. The absence of clinical studies supporting the efficacy of melatonin combined with plant extracts in these formulations raises concerns about their evidence-based effectiveness. Medicines contain 2 to 3 mg of melatonin per tablet, either immediate or modified release. Melatonin intoxication occurs mainly in children, with a higher prevalence between the first year of life and the age of four. Food supplements containing melatonin and plant extracts should be more carefully studied, including the potential adverse effects.

Abstract in English:

Abstract This study is committed to searching for inhibitors of deacetylase SIRT2 within the natural product database via computer-aided drug design techniques. A comprehensive computer-aided drug design platform has been successfully established by integrating various techniques such as drug-likeness screening, pharmacokinetic prediction, molecular docking, and molecular dynamics simulation. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (YaTCM) has been thoroughly explored to identify SIRT2 inhibitors, and the discovered compounds have been validated using molecular dynamics simulation. Through the computer-aided drug design method, five compounds capable of binding to SIRT2 have been successfully screened out from 47,696 natural product compounds derived from 6,220 herbs in the YaTCM database. Molecular dynamics simulation reveals that Artonin E and Paleatin B can form stable receptor-ligand complexes in the active pocket of SIRT2 inhibitors. Based on computer-aided drug design and virtual screening and verification techniques, Artonin E and Paleatin B have been identified as inhibitors of SIRT2, which is a key therapeutic target for the treatment of neuroblastoma. Applying computer aided drug design techniques to identify potential drug molecules from natural products holds profound significance for drug research.

Abstract in English:

Abstract Rifampicin (RFP) is used for the treatment of chronic bone tuberculosis owing to its powerful and wide spectrum antibacterial activities. However, effective concentrations of RFP required to treat bone tuberculosis are maintained for a short time in vivo, and adverse reactions and bone defects may occur after surgery. Therefore, the construction of a new drug delivery system to overcome these problems is required. In this study, we designed, constructed, and demonstrated the applicability of a calcium phosphate cement scaffold loaded with RFP liposomes for the treatment of bone tuberculosis. RFP liposomes were prepared using a film dispersion method. The preparation method was optimized using the encapsulation rate as an indicator and the morphology, mean particle size, zeta potential, encapsulation rate, and drug loading of RFP liposomes were characterized. Calcium phosphate cement scaffolds were constructed using 3D printing technology and used as RFP liposome carriers for sustained-release drug delivery. Finally, some of the properties were verified in vivo through experiments in rabbits. The results indicated that composite scaffolds can provide sustained drug release and are a promising treatment option for bone tuberculosis.

Abstract in English:

Abstract Sjögren’s syndrome (SS) damages exocrine glands, and Lilium brownii var. viridulum Baker (Lilii Bulbus, LB) shows potential as a therapeutic agent. This study evaluated LB’s efficacy in alleviating xerostomia using non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and human salivary gland acinar (NS-SV-AC) cells. In vitro, NS-SV-AC cells were treated with LB (1, 5, 10, 50, and 100 µg/mL) and 5-aza-2′-deoxycytidine (2 µM/mL) for 48 h. Cell viability, fluid secretion, and aquaporin-5 (AQP-5) expression were assessed. In vivo, thirty 20-week-old NOD/SCID mice received LB orally (100, 500, and 1,000 mg/kg) for 4 weeks, with salivary secretion rates measured. AQP-5 and M3 muscarinic acetylcholine receptor (M3R) expression and inflammatory mediator levels were determined using western blotting and enzyme-linked immunosorbent assay. Histopathological examination of salivary glands was also performed. LB significantly increased NS-SV-AC cell proliferation, fluid secretion, and AQP-5 expression. In NOD/SCID mice, LB reduced anti-SSA/Ro and anti-SSB/La antibodies, tumor necrosis factor-α, interferon-γ, and interleukin-6, while increasing AQP-5 and M3R expression. This resulted in increased salivary secretion and reduced glandular inflammation. LB extract appears promising for managing oral health by enhancing salivation, upregulating AQP-5, and modulating immune-inflammatory responses.

Abstract in English:

Abstract Colorectal cancer (CRC) is the third leading cause of cancer death in the world, and its incidence is steadily rising in developing nations. Cell cycle aberrations due to deregulation of cyclin dependent kinases (CDKs) and cyclins are common events during colorectal carcinogenesis. Herein, we investigate the anticancer potential of two multitarget CDK inhibitors viz. roscovitine (specific inhibitor of CDK1, 2, 7, and 9) and UCN-01 (pan CDK inhibitor) against three CRC cell lines. Both the drugs exerted cytotoxicity and inhibited clonogenic potential of human CRC cell lines. These drugs induced apoptosis, downregulated cell cycle regulatory and transcriptional CDKs and cyclins’ protein expression as well as their activity. Moreover, dual combination of either of these CDK inhibitors with standard chemotherapeutic drugs was found to be synergistic in CRC cells. Thus, we demonstrate that multiple CDK inhibition offers promising therapeutic strategy against CRC.

Abstract in English:

Abstract Considering the unique role of medicinal chemistry in the pharmacists’ formation, in this work we assessed the impact of medicinal chemistry teaching on the interpretation of a clinical situation using statistical and learning gain analysis. Lectures were conducted with or without medicinal chemistry information about the drugs involved, and pre and post-tests were applied. Pharmacy students (n = 35) were divided into two experimental groups (control and test) and presented with a case report selected from literature involving statin-related myopathy when a pre-test was applied. A lecture containing pharmacological information on statins was delivered to the students from the control group. In contrast, the test group received the same information, but medicinal chemistry elements of statins were inserted, and afterward post-test was applied. The scores from the pre-test and post-test were statistically evaluated and used to calculate Cohen’s d, Hake’s, and Dellwo’s G learning gains to compare the performance of the students from both groups. The results showed that students from the test group obtained significantly higher performance in the post-test and higher learning gain values. In summary, medicinal chemistry elements provided important knowledge to unveil the reported clinical situation and to provide skills for adequate drug selection to avoid statin-related myopathy.

Abstract in English:

Abstract Cancer is defined as a group of diseases in which abnormal cells multiply and can invade other organs, requiring continuous studies for new drugs. A series of 177 imidazo[1,2-a]pyridine and imidazo[1,2-a] pyrazine synthetic derivatives were previously obtained, and their anti-melanoma IC50 values have been determined. Here, Artificial Intelligence algorithms were used to select molecular descriptors and build a QSAR model, highlighting structural characteristics related to enhanced molecular potency. Additionally, the imidazopyrazine nucleus was compared to a known inhibitor of the Aurora Kinase enzyme, an important target in cancer therapy. Thus, strategic imidazopyrazines were subjected to comparative molecular dynamics calculations, providing inferences about their possible mechanisms of action. The QSAR model allows for the design and prediction of nine new analogues with favourable predicted IC50 values. Molecular dynamics simulations and the estimated binding energies are consistent with the ranking of activities presented by representatives of the series.

Abstract in English:

Abstract This study was aimed to determine occupational and non-occupational exposure to benzene, toluene p-m-o-xylene (BTEXs) and butyl-acetate (nBA). The aim of this work was to develop a simple, sensitive, and reliable chromatographic method using urine, a non-invasive human sample. The method was applied to samples collected from furniture spray workers (n=53) who are at risk of exposure to BTEXs and nBA and office workers (n=51) who have no known exposure risk. Method validation tests, include the sensitivity (LOD≤0.018 ng/mL), precision (RSD≤4.1), accuracy (RE% (-3.9)-4.7), recovery (96.1-103.8%) and linearity (r2≥0.999). Urinary benzene (1.77 vs 1.23 ng/mL, exposed-control, respectively), toluene (51.22 vs 0.77 ng/mL), ethylbenzene (9.25 vs 6.69 ng/mL), para-xylene (1.73 vs 0.62 ng/mL), meta-xylene (2.58 vs 1.20 ng/mL), ortho-xylene (1.61 vs 0.88 ng/ mL), and butyl acetate (33.14 vs 1.63 ng/mL) concentrations were determined in the exposed and control group samples. Significant correlations were found between benzene (p=0.286*), ethylbenzene (p=0.552***) and o-xylene (p=0.292*) levels and smoking status in samples belonging to the control group. The occupationally-exposure-risk group samples have significantly higher BTEXs and nBA concentrations than the control (p<0.001). It was determined that smoking was a significantly effective factor in exposure to benzene, ethylbenzene and o-xylene in the control group.

Abstract in English:

Abstract This is a commentary manuscript, which aims to carry out a critical analysis of the effects of Pharmaceutical Care (PC) without the continuity of the service by healthcare professionals. PC has proven to be a very effective practice for improving pharmacotherapy for medicine users. In Brazil, it is noticeable that in the vast majority of cases, PC is carried out by professionals who are already working within the healthcare systems under the supervision of researchers affiliated with universities, for the purpose of research and data collection. When the research ends there is no continuation of the service, which hinders its continuous implementation and the establishment of a connection with the community. It was observed that after discharge from pharmacotherapeutic monitoring, due to the interruption of the service, there was a deterioration in the clinical and laboratory parameters of individuals with chronic diseases. Therefore, it is clear that PC needs to be implemented not only for research purposes, but also in the “real world”, so that it is long-lasting and permanent with the monitoring of the patients using medication.

Abstract in English:

Abstract In this study, we investigated the cerebroprotective effects of fenchone (FEN) against brain ischemia through in silico and in vivo approaches, focusing on the inhibition of nitric oxide synthase (NOS) and the modulation of oxidative stress markers. Molecular docking revealed the potential binding affinity of FEN for the NOS active site, with a binding energy of -6.6 kcal/mol. This was validated through molecular dynamics simulations over a 100 ns time frame, demonstrating stability and favorable interaction profiles. Wistar albino rats underwent bilateral common carotid artery occlusion/reperfusion (BCCAO/R) followed by FEN administration at doses of 100 and 200 mg/kg. Our results indicated a significant reduction in cerebral infarction size and improvements in electroencephalography (EEG) signal magnitude with FEN treatment. Additionally, FEN restored the activity of antioxidant enzymes (catalase and superoxide dismutase) and decreased malondialdehyde (MDA) and nitric oxide (NO) levels and infarct size compared to those in untreated ischemic rats. Histological analysis further corroborated the neuroprotective effects of FEN, demonstrating the structural preservation of neurons in the hippocampal CA1 region. Overall, the results suggest that FEN plays a neuroprotective role in brain ischemia, potentially through the inhibition of NOS, reduction of oxidative stress, and modulation of antioxidants, highlighting the potential of FEN as a therapeutic candidate for ischemic stroke management.

Abstract in English:

Abstract Pathogenic strains of Escherichia coli can cause gastrointestinal infections, urinary tract infections (UTIs), bacteremia, and other severe infections. Some isolates of this species are capable of producing extended-spectrum β-lactamase (ESBL) enzymes, which mediate resistance against penicillin derivates and cephalosporins. Fungi of the Ascomycota phylum are known to produce antibiotics from different classes with activity against various bacterial agents. Among them, the genera Penicillium, Cephalosporium, Acremonium and Fusidium are known for the production of antimicrobial substances such as penicillin derivates, cephalosporins and fusidic acid. Currently, the search for new antimicrobials produced by species of the Ascomycota phylum includes the assessment of less explored habitats including aquatic environments, extreme environments, and the interior of plants/animals. The genus Penicillium remains promising for the discovery of new antimicrobial substances against resistant bacteria. In addition, those fungi have also been investigated regarding their usefulness for the biosynthesis of nanoparticles with antimicrobial activity. This narrative review introduces clinically relevant Escherichia coli pathovars, the historical contributions of the phylum Ascomycota to the production of antimicrobials, aspects of bioprocesses in the production of antimicrobial metabolites and different approaches of research targeting new antimicrobials such as screenings for fungi in environments not yet studied and the green synthesis mediated by fungi with antimicrobial activity.

Abstract in English:

Abstract This study aimed to analyze the effectiveness of using an antivenom serum (AVS) premedication protocol to prevent early adverse reactions (EAR). This is a cohort study conducted with data from the Londrina Information and Toxicological Assistance Center (CIATox-Londrina) at the University Hospital of the State University of Londrina (HU-UEL), which included patients treated with AVS between January/2017 and December/2021. The independent variable was performing the premedication protocol and the dependent variable was the occurrence of EAR after AVS administration. Patients were followed until hospital discharge. The association analysis was performed with calculation of the Relative Risk (RR) and 95% Confidence Interval (95% CI). A total of 806 cases of accidents with venomous animals were analyzed. The minority (8.1%; n=65) had EAR, and the most frequent symptoms were related to dermatological and respiratory manifestations. The AVS premedication protocol was performed in 96.6% (n=734) of the cases. There was no statistically significant difference in the unadjusted (RR: 1.487; 95% CI: 0.530-4.174) and adjusted (RR: 1.482; 95% CI: 0.522-4.210) models regarding the performance of the AVS premedication protocol and the occurrence of EAR. It is recommended against AVS premedication given the lack of effectiveness in preventing EAR.

Abstract in English:

Abstract The increasing interest in bioactive peptides (BPs) for their potential in disease control and health promotion has been accompanied by a lack of scalable processes for their purification, hindering their commercial production. Membrane filtration, especially using polymeric membranes (PMs), has emerged as a promising technique for BP separation due to its excellent separation performance, ease of fabrication, and flexibility. By utilizing natural sources, such as chitosan, cellulose, lignin, gelatin, alginate, keratin, and silk fibroin, in PM production, the environmental impact of membrane-based separation processes can be reduced while maintaining sustainable, eco-friendly approaches. Natural polymer membranes have exhibited excellent separation performance in terms of molecular weight cut-off and rejection of unwanted compounds, and their performance can be further improved by combining them with nanoparticles or other polymers. This review presents the recent updates on the use of PMs derived from natural sources for the separation of BPs, covering the production and functions of BPs, different membrane separation technologies, and challenges faced during downstream purification.

Abstract in English:

Abstract To evaluate the neuropharmacological profile of new spiro thiazepinone and thiazolidinone compounds in CD1 mice after a computer-aided virtual screening based on a GABA-A/BZD site. From a library of 240 pyrazolo[1,4]thiazepin-3-ones and 39 pyrimidinyl thiazolidin-4-ones, two molecular prototypes of each series were selected by virtual screening using the rank consensus molecular docking approach, based on the GABA-A/BZD site. These compounds, coded as cpTP-0, cpTP-1, TAP-2 and cpTAP-2, were synthesised by multicomponent reactions and evaluated by neuropharmacological screening in CD1 mice (100 mg/kg, p.o.). The study revealed that cpTAP-2 exhibited a significant reduction of immobility time during the forced swimming test (FST), while it did not show any major effects in the rota-rod, open field, plus maze, tail suspension, pentylenetetrazole seizures, and barbiturate sleeping time tests. In a dose-response evaluation, cpTAP-2 reduced immobility time during forced swimming test in CD1 male mice at doses of 100 and 300 mg/kg with biologically relevant effect sizes. These results suggest that cpTAP-2 could elicit antidepressant effects possibly related to GABA-A/benzodiazepine site, although other mechanisms could be implicated.

Abstract in English:

Abstract To synthesize the evidence about pharmacologic treatment of obesity and overweight and to define the options with the best risk-benefit using the stochastic analysis of multicriteria acceptability (SMAA). The analysis addresses a systematic review (PROSPERO CRD42023423308) whose research was realized in PubMed, Scopus, and Web of Science. Randomized controlled trials were included, which verified the effects of sibutramine, orlistat, liraglutide, and semaglutide in patients with IMC ≥ 26 Kg/ m². The risk of bias analysis was performed with RoB 2.0 and the outcomes evaluated were weight loss and serious adverse events. A total of 102 studies with 45.047 participants were included. The network meta-analysis revealed that all the treatments were significantly more effective than the placebo in weight reduction. The use of semaglutide (especially 0.4 mg/day) was associated with a bigger weight loss in comparison to all the other treatments (p<0.05) and the analysis of SMAA showed a risk-benefit of 95%. Besides that, we suggest re-evaluating of sibutramine 10mg/day as a therapeutic option for patients without hypertension or cardiovascular diseases, and we demonstrate the modest weight loss promoted by orlistat 120mg, sibutramine 5mg, and liraglutide 1,8mg and advise against its use, once the benefits do not outweigh the risks.

Abstract in English:

Abstract This study aims to analyze the existence of information about deprescription in the leaflets of proton pump inhibitor (PPI) medications. The leaflets available on the Brazilian Health Regulatory Agency (ANVISA) and Food and Drug Administration (FDA) websites for the following medications were analyzed: omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole. The variables collected in each leaflet were the existence: a) about deprescribing; b) of guidance on the deprescription process; c) maximum recommended time for use; and d) risk of prolonged use. This information was analyzed in accordance with the PPI deprescription guideline, from Canada. Regarding the medication leaflets, 83.33 % from ANVISA and 100 % from the FDA did not present explicit and systematic guidance on deprescribing. Regarding the maximum time of use, 100 % of the leaflets from both agencies contained this information. Regarding the risks of prolonged use of the medication, 33.33 % of the ANVISA leaflets and 33.3 % of the FDA leaflets did not report the increased risks described in the guideline. The results highlight a large gap in information about deprescribing in PPI leaflets; this highlighting is necessary to contribute to the promotion of the rational use of medicines.

Abstract in English:

Abstract Pharmaceutical controlled-release formulations are systems developed by a set of unit operations to achieve a satisfactory combination between a drug and excipients to allow its gradual release. These devices must simultaneously meet criteria for stability, biocompatibility, safety, efficacy, scalability at industrial volumes, and technological efficiency for drug release. Controlled-release systems (CRSs) must release drugs in a way that maintains an adequate concentration in the organism, a requirement that is challenging to meet in practice. Even though novel CRSs may be designed with new materials as excipients, new drugs, or emerging manufacturing technologies, the mechanisms for drug release continue to be governed by a set of similar physicochemical phenomena such as diffusion, swelling, or erosion. These phenomena are too complex to be analyzed by numerical methods; however, they are relatively accessible by probabilistic models especially the Monte Carlo simulation. In this review, we discuss key findings related to the use of this probabilistic method for analyzing the drug-controlled release process in different pharmaceutical devices. Based on this evidence, we propose their potential application in the characterization of new drug-controlled release systems, synergy with other computational methods, and their capability to be adapted for in vivo or in vitro kinetic analysis.

Abstract in English:

Abstract 3D printing, a newer manufacturing technology, is gaining prominence in the pharmaceutical and healthcare sectors, particularly ENT implants. It enables the production of customized biological tissue scaffolds, portable models, and surgical training aids. The emergence of 4D printing offers the potential for enhancing ENT therapy safety and efficacy. The manuscript explores the potential of 3D printing to revolutionize pharmaceutical and clinical practice, enabling the development of personalized drug formulations, patient-centric implants, and anatomical models. This review delves into the emerging concept of “smart” biomaterials used in 4D printing, which are capable of mimicking natural tissues and responding to external stimuli. This paves the way for significant advancements in ENT tissue engineering with the potential to increase treatment safety and efficacy. This highlights the importance of healthcare staff in translating 3D printing innovations into clinical practice for successful adoption. The manuscript highlights the transformative impact of 3D printing in the pharmaceutical and healthcare industries. 3D printing and bioprinting technologies are revolutionizing ENT therapy, offering novel avenues for improved patient care and fostering advancements in the healthcare field.

Abstract in English:

Abstract The landscape of scientific research in Latin America (LA), particularly in the realms of the Physiologically Based Pharmacokinetic (PBPK) and Physiologically Based Biopharmaceutic models (PBPM), is a mosaic of varied contributions, collaborations, and specializations. This study examines research production in the region using data from the Scopus and PubMed databases collected between 2011 and 2023. Brazil stands out as a prominent country in terms of the quantity of publications. When considering thematic specialization, Colombia cones first as the country with the greatest Relative Specialization Index (RSI), followed by Brazil, Cuba, Uruguay, Mexico, and Argentina. Regarding internationalization, Brazil and Mexico are currently exerting significant influence, particularly through their increasing cooperation with the United States and Europe. Interestingly, there is a lack of cooperation inside Latin America at the regional level. Regarding the contribution of Latin-American institutions, the State University of Maringá leads in number of publications, followed by the University of São Paulo and the Federal University of São Paulo. In this work, we analyzed the strengths and weaknesses of LA’s scientific contributions, offering a roadmap for future collaborative and specialized efforts in the field of PBPK and PBBM.

Abstract in English:

Abstract A significant increase in self-medication was observed during the SARS-CoV-2 pandemic, especially among university students due to their higher level of knowledge and awareness, making them more prone to self-medication. Therefore, in this scoping review we aimed to understand the profile of medications used for self-medication among university students during the pandemic, both for COVID-19 prevention and other reasons. We followed the PRISMA-ScR guidelines in conducting the review. The PICo guiding question was, “What is the profile of medications used for self-medication during the COVID-19 pandemic among university students?” Searches were conducted in the Scielo, PubMed, Embase, EBSCOhost, Web of Science, Scopus, BVS, Google Scholar, and CAPES databases based on MESH and DeCS descriptors. A total of 35 studies were selected, with eight (22.8%) reporting self-medication for COVID-19 prevention/treatment ranging from 14-83%, four (11.4%) reporting self-medication for specific symptoms ranging from 11-95%, 19 (54.4%) reporting several reasons for students self-medicating with a range of 50-100%, and four (11.4%) studies not specifying the reason for medication use in self-medication varying from 3-93%. The included studies revealed that the irrational use of medications is a common practice among university students, with varied prevalence of self-medication observed in this population during the COVID-19 pandemic.