Resumo em Inglês:

Abstract We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studies.

Resumo em Inglês:

Abstract A simple, rapid, precise, accurate and sustainable spectrofluorimetric method (SFM) was developed, validated and applied for the determination of 4-aminobenzoic acid and aromatic amino acids (phenylalanine, tryptophan and tyrosine). These compounds are used in biopharmaceutical formulations and therefore must be analyzed by quality control laboratories to meet the criteria established in pharmacopoeias. In general, potentiometric titration (PT) is described in the compendia as the official analytical technique. However, this method showed low sensitivity and selectivity, and moreover was performed with a non-aqueous solvent (acetic acid), which led to higher consumption of reagents and consequently to the formation of residues. Therefore, the SFM was developed in aqueous medium at pH 7.2 using phosphate buffer. It was successfully validated according to the ICH guidelines and showed good linearity range (r>0.999), specificity, accuracy and precision (within and between days) and robustness. The test results were compared between the SFM and PT using raw material samples, while according to the F- and t-tests at 95% confidence level, no statistical difference was found between the methods.

Resumo em Inglês:

Abstract Humans are exposed to natural compounds such as phytoestrogens primarily through diet and supplements. These compounds promote health by alleviating the symptoms and illnesses associated with menopause and arthritis. Diosgenin (DSG) occurs naturally in plants such as Dioscorea villosa (DV) and binds to estrogen receptors, so it may have similar effects to this hormone, including against arthritis. Thus, we investigated the effect of chronic treatment with dry extract of DV and its phytoestrogen DSG on ovariectomized mice with arthritis. We found that dry extract of Dioscorea villosa (DV) contains the phytoestrogen diosgenin (DSG) in its composition. Furthermore, arthritic mice treated with DV and DSG showed reduced neutrophil accumulation in the articular cartilage. Also, the dry extract of DV administered orally (v.o) did not alter the leukocyte count in the joints or promote changes in the reproductive tract. However, DSG altered these parameters, with possible beneficial effects by reducing symptoms related to reproductive aging. Thus, oral treatment with dry extract of DV and subcutaneous (s.c) treatment with DSG showed promise by acting against inflammation caused by arthritis and reducing symptoms in the reproductive tract due to menopause.

Resumo em Inglês:

Abstract The last decade provided significant advances in the understanding of microbiota and its role in human health. Probiotics are live microorganisms with proven benefits for the host and were mostly studied in the context of gut health, but they can also confer significant benefits for oral health, mainly in the treatment of gingivitis. Postbiotics are cell-free extracts and metabolites of microorganisms which can provide additional preventive and therapeutic value for human health. This opens opportunities for new preventive or therapeutic formulations for oral administration. The microorganisms that colonize the oral cavity, their role in oral health and disease, as well as the probiotics and postbiotics which could have beneficial effects in this complex environment were discussed. The aim of this study was to review, analyse and discuss novel probiotic and postbiotic formulations intended for oral administration that could be of great preventive and therapeutic importance. A special attention has been put on the formulation of the pharmaceutical dosage forms that are expected to provide new benefits for the patients and technological advantages relevant for industry. An adequate dosage form could significantly enhance the efficiency of these products.

Resumo em Inglês:

Abstract This study presents the first preliminary phytochemical screening and investigation of the lipoidal matter of Latania verschaffeltii Lem. leaves, belonging to the Arecaceae family. Gas chromatography coupled with mass spectroscopy (GC/MS) was used to analyze and identify compounds of saponifiable and unsaponifiable content. The preliminary phytochemical screening of total methanolic extract of Latania verschaffeltii Lem. leaves revealed the presence of unsaturated sterols and/or triterpenes, carbohydrates and/or glycosides, flavonoids, tannins, saponins, and phenolic acids in the leaves. However, cardenolides, cyanogenic compounds, alkaloids, and iridoids were not detected. The results of the gas chromatography/mass spectrometry (GC/MS) analysis indicated that the percentage of saturated fatty acids (83.82%) is higher than that of unsaturated fatty acids (9.42%). The predominant methyl ester of a saturated fatty acid detected in the sample was hexadecanoic acid methyl ester, accounting for 41.68% of the total. The composition of the unsaponifiable matter consisted of hydrocarbons (5.66%), fatty alcohols (0.96%), terpenes (85.97%), and sterols (2.18%). The major terpenes observed were phytol (43.62%) and squalene (39.27%).

Resumo em Inglês:

Abstract Prostate cancer (PCa) is a highly prevalent condition among men worldwide, resulting in reduced quality of life and increased costs to health systems due to hospitalization and death. This study aimed to explore and understand the evolution of PCa in Brazil from 2008 to 2018. Data were obtained from the National Health System Department of Informatics (DATASUS) using code C61 for malignant prostatic neoplasms. We presented the hospitalization and mortality rates in a temporal-, regional- and age-dependent manner. From 2008 to 2018, a year-dependent increase in hospital admissions due to PCa was reported in Brazil, in which the Southeast region showed the highest prevalence. Men aged ≥80 and those 70-79 years old had similar hospitalization rates, followed by men aged 60-69, 50-59, 40-49 and 30-39 years old. Similarly, an increase in deaths due to PCa was reported during this period, with the highest rates seen in the Southeast. Men aged ≥80 years had higher mortality rates, followed by those aged 70-79, 60-69, 50-59, 40-49 and 30-39 years old. The results obtained indicate an age- and region-dependent increase in PCa morbidity and mortality in Brazil overtime and may contribute to the ongoing discussion on the role and future perspective of the health care system in Brazil.

Resumo em Inglês:

Abstract There are a limited number of studies examining the effects of the pandemic on the daily lives of Turkish community pharmacists, and no research investigating the impact on the lives of Turkish hospital pharmacists has been found. This study aimed to examine the effects of the pandemic on the personal and professional lives of Turkish community pharmacists and hospital pharmacists. In this qualitative study design, a comprehensive set of interviews was conducted with a total of 13 community pharmacists and 7 hospital pharmacists, employing a semi-structured interview guide. Through thematic content analysis of the interviews, four main themes, 1) long-term impacts, 2) dealing strategies, 3) professional life impacts, 4) personal life impacts, have emerged for both community pharmacists and hospital pharmacists. In addition to the psychological impacts and supply chain issues commonly mentioned in the literature, the study revealed ongoing effects such as the inability to sell available products and economic difficulties. Also, the increased demand for over-the-counter products during the pandemic highlights the need for the government to develop policies to address this issue.

Resumo em Inglês:

Abstract Glioblastoma multiforme is a tumor of the central nervous system. Focal Adhesion Kinase (FAK) and αB-crystalline are two proteins involved in glioblastoma development. In this study, we investigated whether the FAK/αB-crystalline interaction is important for glioblastoma cells, we aimed to investigate the interaction of these two proteins in the glioblastoma multiforme cell line U87-MG. Two peptides named FP01 peptide (derived from αB-crystalline) and FP02 peptide (derived from FAK) were synthesized for this study. Treatment of U87-MG with the peptides FP01 and FP02 in the concentration at 50 µM reduced the viability cellular to around 41% and 51%, respectively. Morphological alterations in the cells treated with the peptides when compared to the control were observed. This study suggests that the interaction between FAK and αB-crystalline is important for the viability of glioblastoma cells.

Resumo em Inglês:

Abstract We investigated the vasodilatory effects of Hymenaea rubriflora Ducke stem bark extract (HR- HAc). Vascular reactivity of the aortic rings of Wistar rats was tested by in vitro cumulative doses (0.1 - 729 μg/mL). Rats (n=5) were treated with 25 (G25), 50 (G50) and 100 (G100) mg/ kg of HR-HAc or saline (control group - CG) for four weeks. An in vitro assay resulted in dose-dependent relaxation of the aortic rings with functional endothelium, which was inhibited in the presence of L-NAME. Rings of the treated animals increased acetylcholine relaxing potency at all doses, with a greater effect on G50 (pD2 = 7.8±0.1, Emax = 95.6±1.1) and a decreased contractile potency to phenylephrine in G25 (pD2 = 6.9±0.06, Emax = 61.5±6.0%) and G50 (pD2= 6.6±0.06, Emax = 71.0±8.5%) when compared to the CG in the presence and absence of endothelium (pD2= 6.4± 0.1, 6.4±0.1 and 6.9±0.1, respectively). Cumulative doses of nitroprusside resulted in increased relaxing potency in all treated groups and maintained Emax at 100%. It is concluded that HR-HAc has vasorelaxant capacity and inhibitory vascular contraction activity applied either directly to aortic rings or after treatment with in vivo supplementation, which places this extract as a potential nutraceutical or pharmacological agent for treating diseases associated with vascular dysfunction.

Resumo em Inglês:

Abstract A novel, simple and sensitive high-performance liquid chromatography with fluorescence detection method was developed and validated for the characterization of the preclinical pharmacokinetics of melatonin under pregnant conditions. Plasma samples (25 µL) were treated with 30 µL of ethanol absolute (containing the internal standard, IS). After a centrifugation process, aliquots of supernant (5 µL) were injected into the chromatographic system. Compounds were eluted on a Xbridge C18 (150 mm x 4.6 mm i.d., 5 µm particle size) maintained at 30°C. The mobile phase consisted in a mixture of aqueous solution of 0.4% phosphoric acid and acetonitrile (70:30 v/v). The wavelengths were set at 305 nm (excitation) and 408 nm (emission) and the total analysis time was 8 min/sample. All validation tests were obtained with accuracy and precision, according to FDA guidelines, over the concentration range of 0.005-20 µg/mL. Pharmacokinetic study showed that melatonin systemic exposure increased from day 14, with a significant difference at 19 days of gestation compared to the control group. Our findings suggest a decreased metabolism of melatonin as result of temporary physiological changes that occur throughout pregnancy. However, other maternal physiological changes cannot be ruled out.

Resumo em Inglês:

Abstract The goal of this work is to identify new fatty acid-mimetic 99mTc-complexes to be used as myocardial imaging agents that allow studying heart abnormalities in high-risk patients. In this sense, we designed a fatty acid-mimetic substructure including an amide moiety that, among other properties, could improve myocardial residence time. A diamide with a chain length of 15 atoms and porting a 6-hydrazinonicotinyl (HYNIC) chelator, and an analog with a short carbon-chain, were prepared with convergent organic synthetic procedures and radiolabeled with 99mTc using tricine as the sole coligand. The in vivo proofs of concept were performed using healthy mice. The new 99mTc-complexes were obtained with adequate radiochemical purity. The lipophilicities were in agreement with the length of the chains. While both 99mTc-complexes showed uptake in the myocardial muscle, the designed radiopharmaceutical with the longest chain length had preferential target-uptake and target-retention compared to other complexes described in the bibliography. Further studies, involving imaging assays, synthetic modifications, and assay of new coligands for 99mTc-HYNIC complexes, are currently ongoing.

Resumo em Inglês:

Abstract The quality, efficacy, and safety of medicines are usually verified by analytical results. Measurement uncertainty is a critical aspect for the reliability of these analytical results. The pharmacopeial compendia usually adopt a simple acceptance rule that does not consider information from measurement uncertainty. In this work, we compared decision-making using simple acceptance and decision rules with the use of guard-band for multiparameter evaluation of ofloxacin ophthalmic solution and acyclovir topical cream. Ciprofloxacin ophthalmic solution and acyclovir topical cream samples were subject to pharmacopeial tests and assays. Multivariate guard-band widths were calculated by multiplying the standard uncertainty (u) by an appropriate multivariate coverage factor (k’). The multivariate coverage factor (k’) was obtained by the Monte Carlo method. According to the simple acceptance rule, all the results obtained for ciprofloxacin ophthalmic solution and acyclovir topical cream are within the specification limits. However, the risk of false conformity decisions increases for ciprofloxacin tests. Decisions made using the simple acceptance rule and decision rules with the use of guard-band may differ. The simple acceptance rule may increase the risk of false conformity decisions when the measured value is close to the regulatory specification limits and/or when the measurement uncertainty value is inappropriately high. Nevertheless, the guard-band decision rule will always reduce the risk of false conformity decisions. Therefore, using information on measurement uncertainty in conformity assessment is highly recommended to ensure the proper efficacy, safety, and quality of medicines.

Resumo em Inglês:

Abstract Medicines must be subject to physical, chemical, and biological analysis to guarantee their quality, safety, and effectiveness. Despite the efforts to ensure the reliability of analytical results, some uncertainty will always be associated with the measured value, which can lead to false decisions regarding conformity/non-conformity assessment. This work aims to calculate the specific risk of false decisions regarding conformity/non-conformity of acetaminophen oral solution dosage form. The acetaminophen samples from five different manufacturers (A, B, C, D, and E) were subject to an active pharmaceutical ingredient assay, density test, and dose per drop test according to the official compendia. Based on measured values and their respective uncertainties, the risk values were calculated using the Monte Carlo method implemented in an MS Excel spreadsheet. The results for two acetaminophen oral solution samples (C and D) provided an increased total risk value of false acceptance (33.1% and 9.6% for C and D, respectively). On the other hand, the results for the other three acetaminophen samples (A, B, and E) provided a negligible risk of false acceptance (0.004%, 0.025%, and 0.045% for A, B, and E, respectively). This indicates that measurement uncertainty is very relevant when a conformity assessment is carried out, and information on the risks of false decisions is essential to ensure proper decisions.

Resumo em Inglês:

Abstract Alzheimer’s disease is a devastating neurodegenerative disorder characterized by memory loss and cognitive decline. New AD treatments are essential, and drug repositioning is a promising approach. In this study, we combined ligand-based and structure-based approaches to identify potential candidates among FDA-approved drugs for AD treatment. We used the human acetylcholinesterase receptor structure (PDB ID: 4EY7) and applied Rapid Overlay of Chemical Structures and Swiss Similarity for ligand-based screening.Computational shape-based screening revealed 20 out of 760 FDA approved drugs with promising structural similarity to Donepezil, an AD treatment AChE inhibitor and query molecule. The screened hits were further analyzed using docking analysis with Autodock Vina and Schrodinger glide. Predicted binding affinities of hits to AChE receptor guided prioritization of potential drug candidates. Doxazosin, Oxypertine, Cyclopenthiazide, Mestranol, and Terazosin exhibited favorable properties in shape similarity, docking energy, and molecular dynamics stability.Molecular dynamics simulations confirmed the stability of the complexes over 100 ns. Binding free energy analysis using MM-GBSA indicated favourable binding energies for the selected drugs. ADME, formulation studies offered insights into therapeutic applications and predicted toxicity.This comprehensive computational approach identified potential FDA-approved drugs (especially Doxazosin) as candidates for repurposing in AD treatment, warranting further investigation and clinical assessment.

Resumo em Inglês:

Abstract For places where non-sterile drug production occurs, regulatory bodies recommend monitoring of the environmental bioburden. This procedure provides information regarding possible microbiological risks to which the products may be exposed, so that subsequent action measures may be implemented. The aim of the present work was to quantify and characterize the microorganisms present in Grade D (ISO 8) cleanrooms of a Brazilian pharmaceutical industry, identifying any possible seasonal climatic influences on these environments. Sampling was performed by surface and air monitoring, over 12 months during the year 2019, in rooms that were in operation. For both sampling methods, no statistically significant differences in bacteria and fungi counts were found between months or seasonal periods. Microorganisms that presented higher incidence included Staphylococcus epidermidis (15%) and Micrococcus spp. (13%), common to the human microbiota, and the fungi Cladosporium sp. (23%) and Penicillium sp. (21%), typical of the external environment. The results showed that microbial contamination in the Grade D cleanrooms was within the permissible maximum levels and remained similar throughout the year. Microbiological quality control in the clean areas of the pharmaceutical industry investigated was considered effective, with regular maintenance being necessary to keep bioburden levels controlled.

Resumo em Inglês:

GRAPHICAL ABSTRACT The treatment of fungal infections presents problems in relation to toxicity, pharmacokinetic properties, and undesirable side effects among other factors. An alternative to clarify some of these problems is the use of mathematical modeling and simulation of the pharmacokinetics and pharmacodynamics data of antifungals, in order to seek greater support in decision making regarding the treatment of Cryptococcus infection. Here, we describe the results of a literature review focusing on studies that used mathematical modeling and simulation of pharmacokinetic and pharmacodynamic data of antifungals used in the treatment of cryptococcosis. Through this review, it was possible to identify that most of the content presented refers to studies of modeling, which refer to two very important modeling approaches that provide subsidies for an adequate treatment. Studies that performed Monte Carlo simulations and evaluated the probability of reaching the target show that many treatments used are ineffective, and it is necessary to investigate new models that include more information about these difficult to treat infections. These mathematical tools are extremely important, because through the correlation of pharmacokinetics and pharmacodynamics data of an antifungal, it is possible to make an appropriate decision for the treatment of fungal infections caused by Cryptococcus spp.

Resumo em Inglês:

Constipation is a disorder of the gastrointestinal (GI) and some of the main etiological mechanisms are directly related to changes in GI physiology. The capacity to carry out paired assessments and measure GI parameters under the influence of constipation is a relevant point in selecting a suitable methodology. We aimed to perform a non-invasive investigation of gastrointestinal motility in constipated rats using the alternating current biosusceptometry system (ACB). The animals were split into two groups: the pre-induction stage (CONTROL) and post-induction loperamide stage (LOP). We assessed GI motility parameters using the ACB system. Colon morphometric and immunohistochemical analyses were performed for biomarkers (C-kit) for interstitial cells of Cajal (ICC). Our results showed a significant increase in gastrointestinal transit in the LOP group in addition to a reduction in the dominant frequency of gastric contraction and an arrhythmic profile. A change in colonic contractility profiles was observed, indicating colonic dysmotility in the LOP group. We found a reduction in the number of biomarkers for intestinal cells of Cajal (ICC) in the LOP group. The ACB system can evaluate transit irregularities and their degrees of severity, while also supporting research into novel, safer, and more efficient treatments for constipation.

Resumo em Inglês:

Abstract For good wound management, simultaneous phases during the wound healing process must be considered, including protection against infection, modulation of the inflammatory process, and proliferation and acceleration of cell migration. The aim of this study was to obtain Poly (Vinyl Pyrrolidone) (PVP) hydrophilic fibers containing polyhexamethylene biguanide (PHMB) and hyaluronic acid (HA) using the electrospinning technique to improve chronic wound treatment. Polymers mean hydrodynamic radius and polydispersity index (PdI) were measured by dynamic light scattering (DLS), whereas fiber morphology and diameter were evaluated by scanning electron microscopy (SEM). Also, Fourier transform infrared spectroscopy (FTIR) and contact angle measurements were performed. Fibers were obtained and presented homogenous morphology with a smooth surface. The FTIR study demonstrated an interaction between C=O groups of PVP and HA/PHMB in the PVP + HA/PHMB fibrous composites. Contact angle analysis has shown a hydrophilic characteristic of fibers produced. These findings demonstrate the great potential of electrospinning for developing drug-delivery systems with antimicrobial properties for wound healing treatment.

Resumo em Inglês:

Abstract The expression of PKCε, a member of the protein kinase C family, has been found to be decreased in the frontal cortex of patients with Alzheimer’s disease (AD). Bryostatin-1 is a PKCε activator and has shown benefits in AD animal models. However, how Bryo-1 protects neuronal activity and synaptic function in AD pathology is still unknown. In the present study, we first established an Aβ toxicity cell model by administering Aβ 25-35 oligomers to cultured primary hippocampal neurons. We then evaluated the protective effect of Bryo-1 on this model by administering Bryo-1 together with Aβ oligomers. Finally, we investigated the autophagic influx of primary hippocampal neurons in the presence of Aβ oligomers and Bryo-1. Imaging and electrophysiology recordings showed that Bryo-1 protected synaptic dynamics and functions against the neurotoxicity of Aβ oligomers. Furthermore, Bryo-1 was also found to rescue autophagy influx that was impaired by Aβ oligomer treatment. This discovery may explain the beneficial effects of Bryo-1 in AD animal models. In summary, we discovered a novel mechanism by which Bryo-1 protects neurons against Aβ oligomer-induced neurotoxicity. Our results may support the concept of developing PKCε activators as therapeutics for AD.

Resumo em Inglês:

Abstract Luffa operculata (L.) Cogn. (Cucurbitaceae) aqueous extract (EBN) was gestationally administered to Wistar rats to evaluate sex-related behavioral changes in young individuals receiving a two-hit stimulus of 1 mg/kg EBN, followed by stress challenge (NYM) or lipopolysaccharide (LPS) exposure. EBN exposition occurred by gavage at gestational days (GDs) 17 to 21, and NYM or LPS was conducted at post-natal day 60 (PND60). Behavior was evaluated in the open field (OF) and light-dark box (LDB) apparatuses. Serum hormones, pro- inflammatory cytokines, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine were measured. The liver and kidneys were histologically evaluated. Male and female young rats responded differently in latency to the light side and locomotion frequency on the dark side, corticosterone (females, LPS), and ACTH (females, stress). Male rats showed improved TNF-α (LPS group) and melatonin (LPS group). No histological or biochemical differences were observed in the liver or kidneys. Female young rats were more resilient to the two-hit-stimulus than the male rats. The gestational administration of EBN to male and female Wistar rats and a second stimulus (stress challenge or LPS exposure) at a young age allowed for discriminating differences in behavior, stress hormones, and cytokines according to the sex of the rat. However, no histological alterations in the liver or kidneys were observed, nor in the AST, ALT, or creatinine levels.

Resumo em Inglês:

Abstract The present work aimed to develop a new method for assessing the content of mixtures of polymorphic forms I and II of the drug Efavirenz (EFV) by vibrational spectroscopic techniques such as Middle (MIR) and Near (NIR) infrared and Raman, using multivariate calibration models. Benchtop and handheld instruments were used for NIR and Raman and a benchtop instrument for MIR. In addition, VIP scores and iPLS, variable selection methods were employed. The infrared techniques showed the best models, with Root Mean Squares Error (RMSE) around 5% (w/w). When MIR and portable NIR instruments were used, this value was lowered to 4% (w/w) with selection of variables by iPLS. Raman spectroscopy showed higher error, even with selection of variables, possibly due to the spot laser size used by instruments and the lack of uniformity of the particle size in the samples. The infrared methods developed were shown to be effective in quantifying polymorphic mixtures of EFV. Given the ease of use of handheld instruments, they may be applied as tools of process analytical technology for monitoring quality control during industrial processing.

Resumo em Inglês:

Abstract Background-Pulmonary arterial hypertension (PAH) increases afterload in the right ventricle (RV), inducing adverse ventricular remodelling. Objective- This study explored the protective effects of thyroid hormones and grape juice on serum biomarkers and proteins related to intermediary metabolism in the RV in a model of PAH. Methods- PAH was induced in Wistar rats via the administration of monocrotaline (60 mg/kg i.p.) and they were subsequently treated with organic grape juice (GJ) and thyroid hormones (TH), administered separately or in combination. Results: The RV systolic diameter significantly increased (20%) in the PAH group compared to the control group (P = 0.002). Total CK, LDH, and ALT levels were reduced (~50%) (P<0.001) in the PAH+TH+GJ group as compared to PAH group. Glucose, albumin, triglyceride, and total cholesterol levels were reduced (~50%) (P<0.001) in the PAH group; however, these parameters returned to baseline in the PAH+GJ group. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein expression increased two-fold (P<0.001) and PDH protein levels were reduced (~25%) in the PAH+TH+GJ group compared to the PAH group (P<0.001). Conclusion: The data suggest that serum biomarkers can help in the evaluation of this disease, and that this therapeutic approach can attenuate maladaptive remodelling in the PAH model.

Resumo em Inglês:

Abstract The Specialized Component of Pharmaceutical Services (CEAF) is a crucial strategy for accessing medicines through the Brazilian Public Health System, holding the highest budgetary impact on outpatient pharmaceutical care. This study aimed to assess the association of socioeconomic factors with access to CEAF drugs in municipalities throughout Paraná from 2010 to 2019. It utilized a retrospective, observational, cross-sectional approach, evaluating dispensed medication units, medication expenditure, and average unit cost. Analyses were performed to identify a correlation between the use of CEAF drugs and socioeconomic indicators. In these 10 years, the number of dispensed units practically quadrupled, and the expenditure on these drugs doubled, from BRL 214 million to BRL 476 million. The Index of Paraná Institute for Economic and Social Development of Municipal Performance (IPDM) showed a greater association with the use of CEAF drugs, and no correlation was observed between gross domestic product (GDP) per capita and the municipal population. Overall, the IPDM index that includes income, education, and health are socioeconomic factors that influence the utilization of CEAF drugs. These findings emphasize the need for health education among users and adjustment of public policies to mitigate inequalities in the CEAF drug access for the citizens of Paraná.

Resumo em Inglês:

Abstract Candida albicans is the main fungus responsible for acute and recurrent vaginal infections. Low adherence to treatment is due to dosing frequency and available topical medications. Thus, we developed mucoadhesive tablets based on Schinopsis brasiliensis Engler extract composed of Carboxymethylcellulose (F1), Hydroxypropylmethylcellulose (F2), or Pluronic (F3), against C. albicans . The extract metabolites determination showed presence of polyphenols (15 μg.mg-1), flavonoids (5.51 μg.mg-1), and tannins (4.80 μg.mg-1). The in vitro antifungal activity was performed by broth microdilution method. Quality control tests were performed according international pharmacopeias. Regarding the mucoadhesion test, in terms of the force expressed between the tablet:mucin disc, the average values were approximately 0.1267 N (F1), 0.0411 N (F2) and 0.814 N (F3), while in the tablet:vaginal mucosa, the average values were approximately 0.0294 N (F1), 0.0166 N (F2) and 0.0365 N (F3). The dry extract showed a minimum inhibitory concentration of 62.5 μg.mL-1. In evaluating the in vitro release of tablets, polymers derived from cellulose released 100% in less than 4 hours, while Pluronic released around 56.3% in 72 hours. It is concluded that F1 has greater mucoadhesion while F3 has a modified release rate, providing promising results for future application of the formulation in the clinical assay.

Resumo em Inglês:

Abstract This study attempted to describe the disease modifying therapies (DMTs) use patterns and related adverse events in multiple sclerosis (MS) patients assisted by the Brazilian Unified Health System (SUS). This is a cross-sectional study conducted at a reference center in the Midwestern Brazil. Demographic, socioeconomic, and clinical data, and adverse events associated with DMTs were collected. We observed 291 patients with a mean age of 41.4 years, and mostly (68.6%) women. Most patients (58.8%) were using first-line treatment. Fingolimod (29.9%) and beta interferons (23.7%) were the most used drugs. About 74.2% of patients used DMTs for more than six months. In 26.5% of patients, 238 adverse events were reported, 67.2% of which were mild and 32.8% of which were moderate. The most frequent adverse events were headaches (6.9%), myalgia (3.8%), and flu-like symptoms (3.1%). The proportion of adverse events proportion ranged from 17.3% (natalizumab) to 41.2% (dimethyl fumarate). Most MS patients treated by SUS used first-line DMTs. After adjustment, there was noticed that adverse events associated with DTMs are twice as likely to occur in users of the first-line treatment than other lines (OR 1.99, p=0.01). It is essential to develop DMTs safety monitoring strategies to promote their rational use.

Resumo em Inglês:

Abstract Valproic acid (VPA) is an effective and inexpensive anticonvulsant commonly prescribed as an antiepileptic. However, there is a percentage of susceptible patients who experience unwanted effects, such as weight gain and fatty liver. Ivermectin (IVM), a versatile antiparasitic, has shown potential in the treatment of non-alcoholic fatty liver disease. In this study, the potential hepatoprotective effect of ivermectin on valproic acid-induced hepatotoxicity was investigated in rats. VPA (250 mg/kg/day) was orally administered for 14 consecutive days to induce hepatocellular damage in adult Wistar rats, after which the animals were treated with a subcutaneous injection of IVM (0.4 and 1.3 mg/kg/day) for another five days. Animals receiving VPA developed obesity and microvesicular and macrovesicular steatosis. They also had increased levels of plasma triglycerides and aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase enzymes. IVM treatment significantly decreased serum triglyceride and cholesterol levels and attenuated valproic acid-induced hepatic lipid accumulation in rats. These results were confirmed by histopathological examination.

Resumo em Inglês:

Abstract This descriptive study analyzed the perceptions of Brazilian hospital pharmacists towards their clinical attributions related to “interventions in the prescription” and “monitoring the use of medication” in view of the current Basel Declaration of the International Federation of Pharmacists (Federação Internacional de Farmacêuticos - FIP). Brazilian hospitals of high and medium complexity were identified and a pre-tested questionnaire based on the 65 recommendations of the Basel Statments was sent via e-mail, directed to the pharmacists of the 2,054 hospitals. The results were categorized into: a) they meet the statement, b) they do not meet, or c) they did not respond. Pharmacists from 111 hospitals returned the survey. For the recommendations of the theme “influences on prescribing”, the highest percentage of compliance was related to the effective performance of pharmacists in the Pharmacy and Therapeutics Committee (PTC), which occurred in 54.1% of the hospitals. While for the “monitoring the use of medication” was refered to the existence of an easily accessible system for notifying technical complaints, in 47.7 % of the hospitals. The results emphasize that these activities need to be reviewed and aligned, to offer better quality and more safety to the patient in relation to the use of medication.

Resumo em Inglês:

Abstract This study highlights the importance of fungi, specifically Botrytis cinerea Pers., in the search for bioactive compounds with therapeutic potential. Extraction approaches using Soxhlet, and maceration methods were applied of the fungus to explore secondary metabolites production. The compound mannitol was separated from the crude extract through nuclear magnetic resonance. The results indicated a positive effect on the inhibitory action of the acetylcholinesterase enzyme for ethyl acetate fractions obtained from the broth. Additionally, significant cytotoxic effects were observed in neoplastic cell lines, with IC 50 values of 3.5 μg/mL, 5.6 μg/mL, and 8.5 μg/ mL for colon cancer cells, monocytes, and human glioma, respectively. Antimicrobial activity was also evident in B. cinerea extracts and fractions, particularly in the ethyl acetate fractions from the broth. Larvicidal activity was observed in the chloroform fractions of the broth, with CL50 values of 20,824 μg/mL and 83,401 μg/mL. Furthermore, morphological changes in larvae were observed when exposed to the fungus’s extracts and fractions. The results suggest that B. cinerea extracts and fractions have the potential to identify substances with applications in biological activities, such as cytotoxic, antimicrobial, and larvicidal actions. Continued research is recommended to investigate compounds responsible for these activities and explore their potential applications.

Resumo em Inglês:

Abstract Brazilian Red Propolis is a resinous material produced by Apis mellifera bees through the collection of the exudates of Dalbergia ecastaphyllum , rich in flavonoids, and Symphonia globulifera and Clusia species, which are rich in polyprenylated benzophenones. More than 200 compounds, including flavonoids and polyprenylated benzophenones have been found in Brazilian red propolis. The objective of the present study was to evaluate the chemical composition and antiviral activity of an ethanolic extract of red propolis from Alagoas, Brazil, against Herpes Simplex Virus (HSV-1). In the HPLC-PDA-ESI-MS/MS analysis were detected flavanones, isoflavones, chalcones, pterocarpans and polyprenylated benzophenones. The measurement of antiviral activity of red propolis extract was performed by DNA quantification through quantitative real-time PCR assay and negative staining Electron Microscopy. The pretreatment, post-treatment, and virucide assays using ethanolic extract of red propolis with concentration of 8, 12, 24, 48, or 96 µ g/mL, indicated an inhibition of the viral binding and viral entry into cells as well as the replication of HSV-1. In the electron microscopy imaging was observed the disruption of the viral membrane in the HSV-1 treated with red propolis, when compared with HSV-1 that was treated with phosphate buffered saline alone, indicating that ethanolic extract from red propolis can act directly on the viral envelope, through lipid membrane degradation and/or directly blocking the enriched proteins on the viral surface.

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Abstract Protein tyrosine kinases play a role in the cell signaling pathways involving cell growth, differentiation, apoptosis, and metabolism of cancer cells. Because of that, the molecular docking, molecular dynamics, MM-PBSA, and prediction ADMET properties were conducted to evaluate the inhibition activity of epoxy-thioxanthones against platelet-derived growth factors receptor (PDGFR) and epidermal growth factor receptor (EGFR) proteins. A series of ten thioxanthone compounds bearing hydroxy, epoxy, chloro, and bromo substituents have been designed and evaluated. The docking results showed that the epoxy-thioxanthones ( A-J ) have binding energy from -7.12 to -9.81 and -7.24 to -8.06 kcal/mol against those proteins, respectively. Compared with the native ligands, all epoxy-thioxanthones gave stronger binding energy (-7.24 to -8.06 kcal/mol) with the active site of EGFR than the erlotinib (-7.05 kcal/mol), which is remarkable. This result is also in line with the molecular dynamics results. The calculation of binding energy MM-PBSA that compounds D , E , I , and J had comparable EGFR protein stability to erlotinib. The binding energy of those compounds (-19.29 to -29.35 kcal/mol) had lower than erlotinib (-8.25 kcal/mol). Furthermore, in physicochemical properties prediction, those compounds fulfill Lipinski’s rule parameters and the minimum standard parameters in ADMET properties.

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Abstract Curcuma zedoaria is a traditional medicine used for various purposes in human life. The organic solvent extracts of this plant also exhibit antioxidant, antibacterial, anti-inflammatory, anti- cancer, anti-necrosis, and hepatoprotective properties. However, the prospect of employing this plant extract for skin whitening, particularly its molecular mechanism, has not been reported yet. Therefore, in this study, the total polyphenolic content, antioxidant activity, cytotoxicity, tyrosinase inhibitory, melanin inhibitory, and target gene expression using the ethyl acetate fraction of ethanolic extract from Curcuma zedoaria , were all examined. The TPC result of the sample was 42.18±2.25 mg GAE/g extract with impressive antioxidant activity. Half maximal inhibitory concentration value of 2,2-Diphenyl-1-picrylhydrazyl radical scavenging assay and Ferric reducing antioxidant power FRAP value at a concentration of 2.5 µg/mL were 49.06±0.29 µg/mL and 116±50 μM Fe2+/L, respectively. The extract had no cytotoxicity at 25 µg/mL, inhibited melanin production for 74.02±3.05% and tyrosinase for 137.45±1.38%. In particular, the extract demonstrated the ability to block the expression levels of four melanogenesis-related genes. Moreover, GCMS analysis results also detected 28 different compounds, with two new compounds accounting for a high proportion. These results suggested that C. zedoaria has a significant potential for application in skin-pigmentation treatment cosmetics.

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Abstract To characterize the main pharmaceutical interventions performed by reviewing the pharmacotherapy of hospital patients with COVID-19. This is a study carried out in a hospital center in the northern region of Santa Catarina, in which data were collected on pharmaceutical interventions resulting from the review of the pharmacotherapy of hospital patients with COVID-19, between April 2020 and June 2021. During the study period, a total of 16,675 medical presciptions were validated by pharmacists in theselected hospitalization sectors. These validations resulted in 1,108 pharmaceutical interventions, with the largest number related to drug dose adjustment (25.9%). Among the drugs, the class with the highest number of interventions was antimicrobials, especially Azithromycin with 23.5% of interventions performed, followed by Teicoplanin 23.9% and Meropenem 18.6%. Pharmaceutical interventions due to kidney function were also highlighted, as the disease is not restricted to damage to the respiratory system, but also presents complications in other organs, such as the kidneys. Through the review of pharmacotherapy and the pharmaceutical interventions resulting from this activity, clinical pharmacists played a key role in optimizing pharmacotherapy, in addition to promoting the safe use of medications.

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Abstract In Brazil, hepatitis C virus (HCV) treatment has gone through several stages until it reached the current schemes. This study aimed to evaluate the clinical, epidemiologic, and effectiveness of treatment with second-generation direct-acting antivirals (DAAs) for HCV-infected patients in southern Brazil. Medical records of a reference center of Uruguaiana-RS/Brazil were evaluated from December 2017 to August 2020. Data collected included demographics, disease severity and comorbidities, genotype, viral load, medications, treatment side effects, and sustained virological response (SVR). A multivariate linear regression model was developed to identify the factors associated with non-sustained virological response. The HCV-infected patients were predominantly male, white, Genotype 1, with initial liver fibrosis (F0/F1), and untreated patients. Laboratory parameters of the liver profile showed significant improvement after completion of treatment with second-generation DAA for 12 weeks. Significant results were found in the Genotype where 7.3 and 6.0 times more chances of Genotype 1a and Genotype 3, respectively, to present detectable SVR compared to Genotype 1b. Variable cardiovascular comorbidity also indicated a higher risk of absence of SVR compared to individuals without this comorbidity. Treatment with second-generation DAAs can contribute to the Brazilian hepatitis C elimination plan proposed by the World Health Organization.

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Abstract Betanin is a natural pigment belonging to the group of betalains with vasoconstrictive properties. This study investigated the underlying mechanism involved in the vasoconstrictive effect of betanin in rat aorta. Betanin enhanced the contractile response in aortic rings precontracted with phenylephrine. In aortic preparations under resting tonus, betanin induced potent and sustained contractions. The contractile effect of betanin was increased in endothelium-denuded aortic rings, while treatment of endothelium-intact preparations with the alpha-1-adrenergic receptor antagonist prazosin abolished the contractile effects of betanin. In the presence of verapamil, the contractile effects of betanin were decreased, and they were abolished under Ca 2+ -free solution. Vasoconstriction was not affected by treatment with yohimbine and guanethidine. Betanin partially restored the endothelium-dependent vasorelaxant effect induced by acetylcholine, a response that was blunted in aortic rings treated with baicalin, an inhibitor of the nitric oxide (NO) - cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway. In conclusion, the vasoconstrictive effects of betanin likely involve alpha-1 adrenoceptors and are dependent on endothelial modulation.

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Abstract Numerous studies have focused on microRNAs (miRNAs) in hepatocellular carcinoma (HCC). However, the specific role of miR-135a-5p in HCC has remained unclear. Thus, this study aimed to elucidate the role and mechanisms of action of miR-135a-5p in HCC. Transfected Huh-7 HCC cells were subjected to cell proliferation, apoptosis, migration, and invasion assays to investigate the role of miR-135a-5p and FOXO1 in modulating cellular functions. Additionally, tumor xenografts from nude mice were utilized in vivo to validate the in vitro findings. Downregulation of miR-135a-5p or upregulation of FOXO1 inhibited cell proliferation and metastasis of Huh-7 cells while promoting apoptosis. Conversely, upregulation of miR-135a-5p induced proliferation and metastasis of Huh-7 cells while suppressing apoptosis. Furthermore, FOXO1 was identified as a direct target of miR-135a-5p. Notably, downregulation of miR-135a-5p or upregulation of FOXO1 suppressed tumor growth in Huh-7 cells. Inhibition of miR-135a-5p impeded HCC cell proliferation and metastasis by upregulating FOXO1 expression.

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Abstract Hops ( Humulus lupulus L.) is of notorious importance in the brewing industry, providing bitterness, aroma and acting as a preservative. Besides beer, innovative technologies are being developed on hop extracts, and this review aims to highlight their potential applications in the food, veterinary, and pharmaceutical industries . The emphasized topics include extraction methodologies, bioactive compounds, and motivations for use . Publications from the last 10 years that have claiming promising results, of extracts with verified composition or elucidated extraction methodology, in the development of new products such as: functional foods, food preservative, microbiota control in livestock, drug active ingredient or technological adjuvant were selected. This review collected relevant articles and subjected them to bibliometric mapping of the most common terms found in the title or abstract, in order to understand how the themes evolved in the time series and what the most recent trends are. Most of the claimed applications are related to antimicrobial potential, followed by other pharmacological applications.

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Abstract This study focuses on the extraction, characterization, and application of polysaccharide, Arabinoxylan (AX), derived from barley husk ( Hordeum vulgare ). Arabinoxylan was extracted by alkali extraction method with a significant yield of 26%. It was thoroughly characterized to ascertain its physicochemical properties such as percentage yield, solubility, swelling index, loss on drying, sulphated ash and micromeritics. Afterwards AX was employed as a polymer in the synthesis of controlled-release nanoparticles (NPs) of dexlansoprazole, an acid-labile drug. Ionic gelation and nanoprecipitation methods were employed to prepare various NP formulations, which were characterized using techniques such as zeta sizer, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and thermal analysis. FTIR confirmed the compatibility of nanoparticles while SEM results displayed that AX based nanoparticles were smooth and spherical in shape. Likewise, the thermal analysis revealed that nanoparticles were thermally stable. Furthermore, the AX-based nanoparticles demonstrated efficient entrapment efficiency of 79.59 ± 4.6% and 43.69 ± 4.9%, along with sustained drug release profiles, following Korsmeyer-Peppas models. Ionic gelation method was observed to be comparatively better than nanoprecipitation method. Overall, this study showcases the potential of utilizing AX as cost-effective and renewable biomaterial for the development of polymer-based drug transport system, facilitating efficient and controlled drug delivery.

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Abstract Cutaneous melanoma, a highly aggressive skin cancer, is the leading cause of death among skin neoplasms. Hence, this study focused on developing a 3,3'-diindolylmethane (DIM)-loaded pomegranate oil (PO) nanocapsule suspensions and their potential effects on melanoma cells. Nanocapsule suspensions were prepared by the interfacial deposition method (Eudragit ® RS100). Medium-chain triglyceride (MCT) nanocapsules were produced for comparison. The of nanocapsule suspensions showed nanometric size (<180 nm), low polydispersity index (<0.12) (as measured by dynamic light scattering), positive zeta potential (tested by capillary microelectrophoresis), pH below 5.0 (as measured by potentiometry), DIM content, and nearly 100% encapsulation efficiency (evaluated by HPLC). The formulations were considered non-irritating (according to HET-CAM) regardless of the core constitution. Notably, PO-based nanocapsules showed a superior performance compared to the MCT-containing formulation in delaying DIM light degradation (tested by UVC radiation), lowering genotoxicity (determined by Allium cepa ), and increasing in vitro antioxidant action (measured by ABTS and FRAP). Additionally, the PO-based formulation demonstrated higher in vitro antitumoral activity in B16F10 than MCT nanocarriers (IC 50 of 6.49 and >24 µg/mL, respectively), and antimetastatic capacity by reducing B16F10 cell adhesion, colonization, and migration. Based on these results, this study suggests that the nanoencapsulation of DIM into PO nanocapsules may be a promising approach in melanoma treatment.

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Abstract This cross-sectional study investigated the association of SNPs rs670 (C>T) and rs693 (G>A) with parameters of lipid metabolism and endothelial activation in 167 subjects, including 86 COVID-19 outpatients and 81 healthy subjects (control group) matched for sex and age. Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein cholesterol (non-HDL-c), triglycerides (TG), apolipoproteins (Apo A-I and B), and vascular cell adhesion molecule-1 (VCAM-1) were determined. The SNPs were genotyped by quantitative polymerase chain reaction (qPCR). A p -value<0.05 was assumed. COVID-19 outpatients showed increases in TC (187.0±48.3 vs . 160.8±32.0 mg/dL), LDL-c (110.3±41.5 vs . 98.8±28.2 mg/dL), non-HDL-c (138.3±45.8 vs . 115.6±31.6 mg/dL), TG (139.7±80.3 vs . 84.9±35.1 mg/dL), and Apo A-I (149.5±40.0 vs . 133.3±20.9 mg/dL), along with a high frequency of hypercholesterolemia and hypertriglyceridemia. VCAM-1 levels were double those of the control (682.7±231.8 vs. 299.3±102.9 ng/mL) and a strong predictor of COVID-19 (AUC=0.946). Moreover, VCAM-1 correlated with TC (r = -0.223) and HDL-c (r = -0.225). The decrease in TG and VCAM-1 is predicted by the dominance of the T allele (rs670) and its codominance with the A (rs693) allele in COVID-19 outpatients. COVID-19 has been shown to be associated with dyslipidemias and endothelial activation, and apolipoprotein polymorphisms may influence this.

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Abstract This study examines the adequacy, readability, and quality of the information provided on package inserts for veterinary medicines in Brazil. It aims to identify the essential information required in these documents and assess non-compliance with regulatory standards. Initially, a documentary analysis was conducted to identify mandatory information as per Federal Decree No. 5,053/2004 and Normative Instruction No. 26/2009 of the Ministry of Agriculture, Livestock and Supply. Subsequently, 256 package inserts were analyzed to evaluate their suitability using descriptive quantitative analysis. This analysis showed a lack of essential technical and scientific information, necessary for the rational use of veterinary medicines. Mandatory elements supporting the correct use of veterinary medicines and essential information, such as a qualitative description of excipients, equivalence factors, the mass of active pharmaceutical ingredient per volume (when applicable), and information about the customer service center, were absent from these documents. This study found at least one non-conformity in the 252 evaluated package inserts. These findings underscore the significant lack of adherence to established rules and the low quality of technical-scientific information, reducing the comprehension of both prescribers and owners. The authors highlight the need for regulatory agencies to review and improve the guidelines that govern the format and content of package inserts.

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Abstract Sepsis is characterized by inadequate microvascular tissue perfusion, leading to organ dysfunction and death. Adenosine levels increase during inflammation and tissue hypoxia, potentially influencing cardiovascular parameters through activation of four receptors coupled to the G protein (A 1 , A 2A , A 2B , and A 3 ). Caffeine a non-selective adenosine receptor antagonist and it might prevent the cardiovascular collapse associated with sepsis. This study aimed to assess caffeine effect on sepsis-induced cardiovascular changes in rats. Animals were submitted to cecal ligation and puncture (CLP) to induce sepsis. Two, 8, and 14 hours after the procedure, CLP and sham groups were assigned to receive caffeine (30 mg/kg, s.c.) or vehicle. Twenty-four hours later, biochemical, and hemodynamic parameters were evaluated in addition to survival rate. Sepsis resulted in hypotension, hyporesponsiveness to vasoconstrictors, reduced renal blood flow, and increased blood glucose and lactate levels. Caffeine prevented changes in glycemic levels, but not in the cardiovascular alterations induced by sepsis. Caffeine also shows no discernible impact on markers of organ dysfunction or tissue perfusion. Thus, while caffeine maintained glycemic levels, it did not mitigate sepsis-induced cardiovascular collapse, organ dysfunction, or affect mortality rates. Therefore, caffeine does not provide significant improvements during sepsis.

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Abstract The demand for innovative eco-friendly ingredients is a current trend in the pharmaceutical and cosmetic fields. Starches can be a good alternative because their gelatinization property could increase the stability of emulsions. The objective of the present study was to develop a gel formulation based on tapioca and corn starch and to evaluate its stability, physical-mechanical and sensory properties according to the experimental design. A general full factorial experimental design with three levels was elaborated for each polysaccharide under study. The best formulation was evaluated in terms of rheological and sensorial properties. Only the formulation with tapioca and corn starch in combination was stable, showing a thixotropic behavior without changes in rheological parameters after 28 days. Sensorial analysis classified the formulation as soft, easy to spread and giving a hydration sensation. The nature of the polymers could be responsible for a synergistic effect on the spreadability parameter. According to the results obtained, the use of starches for the development of topical products can be suggested as a natural alternative to the polymers and silicones commonly used as rheological additives. The developed formulation could be a green alternative with proven physical-mechanical stability and excellent sensorial properties.

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Abstract Caffeine consumption by academics, especially those in medical school, is done indiscriminately due to the need to reduce fatigue during their activities and, consequently, increasing their performance. Although it seems to be a harmless practice, it can be related to some health problems. Among these other damages are: arrhythmias, urinary incontinence, loss of appetite, nausea, increased blood pressure, insomnia and sudden death. In this context, this work evaluated cardiovascular damage associated to long-term use of caffeine based on clinical evaluation of students aged 18 years or older in a private medical college in Espírito Santo. Analysis was performed through a brief questionnaire followed by assessment of heart rate and blood pressure. The work was performed with 26 men and 69 women and an average of 70% of the population claimed to consume caffeine. It was also seen that among the students who had the greatest changes in relation to blood pressure were those who were in the 1st and 3rd years of the course. In short, no significant changes were observed in relation to caffeine consumption throughout graduation or cardiovascular impacts associated with its use. However, the evaluated individuals are mostly young and the study follow-up time was short.

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Abstract This study aimed to describe the pattern of antimicrobial agent usage in a general tertiary care hospital in Rio de Janeiro. Some prescriptions were evaluated for its therapeutic indication, dose, route of administration, and duration of treatment based on Antimicrobial Application Sheets and daily medical prescriptions. Consumption was expressed by using Defined Daily Dose per 100 bed-days. Within the 20,182 validated prescriptions, 9,356 were eligible for the study. The first-choice therapy was prescribed 6,175 (66.01%) times. It was verified that 5,455 (58.31%) of the prescribed antimicrobial agents were associated with bacteriologic culture tests, and among 2,484 (45.54%) of such cultures, at least one microorganism was identified. Negative results were obtained in 2,971 (54.46%) processed cultures, in which 1,289 patients (43.49%) had already initiated antimicrobial therapy. From patients with negative cultures, 518 (33.99%) prescriptions had alternative treatments, and from these, 495 (95.96%) could have been changed. Therefore, de-escalation of antimicrobial therapy has not been a practice in the institution. Among prescriptions that needed renal function dose adjustments, this was performed in 81.11%. In general, prescriptions were adjusted for dose (70.03%), route of administration (99.63%) and duration of treatment (74.70%). Piperacillin/tazobactam was the mostly used antimicrobial (3,923 DDD/100 bed-days).

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Abstract The pharmaceutical industry is mostly dedicated to the production of drugs in solid forms such as tablets and capsules with active ingredients and excipients in the same physical state. Regarding the regulatory requirements for the analytical development and implementation of solid-state analyses, internationally recognized pharmaceutical compendia play an important role. However, the information contained in the various general chapters and monographs differs from each other, especially in countries that have national pharmacopeias, such as Brazil. Thus, the main objective of this work is to critically evaluate, based on the technical-scientific literature, the harmonization of the United States, European, British, Japanese and Brazilian pharmacopeias with respect to the following analytical techniques used for solid-state characterization: X-ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, and infrared and Raman spectroscopies. The working principle of each analytical technique, as well as the methodological parameters that impact the implementation of the analyses, are detailed. The results indicate that, in terms of solid-state characterization analysis, the adoption of unified scientific standards and principles is not yet a reality for all compendia. Additionally, the lack of harmonization between BrazP and the other compendia is especially significant, considering that ANVISA is an ICH member, the main entity responsible for promoting harmonization.

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Abstract Due to their ability to produce synergistic effects and take a holistic approach to health and wellness, polyherbal formulations have attracted a lot of interest lately. Chewable tablets have distinguished themselves among the available dosage forms as a practical and patient-friendly alternative, especially for people who have trouble swallowing conventional solid oral dose forms. An overview of the development, formulation, therapeutic uses, and difficulties relating to polyherbal chewable tablets are intended by this review article. Chewable polyherbal formulations mix many plant-derived substances, each with distinct therapeutic qualities, to produce a concoction that targets particular health issues. The review article explains the therapeutic uses of polyherbal chewable tablets in a number of medical specialties, including both contemporary herbal therapy and conventional systems like Ayurveda and traditional Chinese medicine.

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Abstract Dissolution tests evaluate the release of therapeutic agents in various dosage forms, acting as quality control tools to secure batch–batch equivalence and guides for formulation development and in vivo drug bioavailability prediction for pharmaceutical scientists. In this article, dissolution tests described in the Brazilian Pharmacopeia 6th ed. were systematically reviewed using the following descriptors: drug, dosage forms, apparatus, rotational speed, dissolution media, sampling time, quantitative procedure, and the value of Q . Test conditions were compared with those described in the United States Pharmacopeia (USP) dissolution database. In September, 2023, dissolution tests were required for 127 monographs, accounting for only 10% of those listed in the USP database. Paddles were used in 80 monographs (63.5%) at various rotation speeds. Basket apparatus was recommended for 47 products, including tablets, capsules, and gastro-resistant granules with variable speed ranges. The simulated gastric fluid was described in four monographs. Moreover, pH of the dissolution media for 29 products was adjusted in the physiological range of 2–7.5. Twenty-eight monographs are exclusively listed in the Brazilian Pharmacopeia. Among the 99 products listed in both compendiums, dissolution tests were only harmonized for 69 monographs.

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Abstract The study aimed to analyze the profile of requests for medicinal cannabis-based products within the Technical Notes (TNs) of the e-NatJus platform. Conducted as a descriptive documentary research, it utilized secondary data from the platform, covering TNs published from 2018 to August 31, 2023. Among the 672 identified TNs, a substantial number, 83 % (n=558), presented unfavorable opinions. The applicants, predominantly male (53.12 %), spanned various age groups from newborns to the elderly. Geographically, requests were distributed across 23 states in Brazil, with Rio Grande do Sul being the most representative (19.6 %). Diagnostic confirmation relied on medical reports, and prevalent diagnoses included "unspecified speech or language development disorder" (CID F80.9) and "epilepsy" (CID G40), accounting for 19.34 % and 18.6 % of TNs, respectively. The findings offer a comprehensive view of the judicialization of health concerning medicinal cannabis in Brazil. In light of divergent results for similar therapeutic goals, the study emphasizes the necessity for clinical guidelines and robust scientific research to ascertain the effectiveness and safety of cannabis-based medications. Clear guidelines are crucial to ensure the effective and safe use of medicinal cannabis in the judicial context.

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Abstract In the biopharmaceutical industry, the conventional “linear and sequential” clinical trial approach is still the norm; however, it is frequently beset by issues with patient selection, retention, and monitoring that are not up to par, leading to longer trial durations and higher trial failure rates. Artificial intelligence (AI) has the potential to reduce the duration of clinical trials significantly, expedite protocol design and study implementation, improve trial outcomes, and lower the cost of biopharmaceutical R&D. AI may also speed up clinical cycle times. Clinical trial mining, design and execution, and real-world experience analysis are all possible using AI. Major drug makers are utilizing AI to locate volunteers for clinical trials or to cut down on the number of subjects required for drug testing, which might speed up medication development and save millions of dollars. The clinical trial procedure may be enhanced by AI, but evidentiary requirements for a drug’s efficacy and safety won’t alter, according to regulators. This article discusses the application of AI, RWD, and RWE in clinical trials and how it is transforming the biopharma value chain, encompassing all pharmaceutical firms referred to as “biopharma companies” due to the inclusion of biologics in their development pipelines and within these biopharma firms, artificial intelligence (AI) is finding its way into drug research.

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Abstract There is currently no consensus on whether to initiate molnupiravir treatment for all outpatients at high risk of severe SARS-CoV-2 infection. PubMed, Embase and Cochrane databases were systematically searched for studies that allocated COVID-19 high-risk, non-hospitalized patients to molnupiravir or a control. We computed risk ratios (RR) for binary endpoints, with 95% confidence intervals (CI), random effects model was used and a p-value <0.05 was considered as statistically significant. We analyzed data into Review Manager 5.4. We included seven randomized studies, with total of 31,569 patients , of whom 15,706 (50.8%) underwent molnupiravir therapy. Molnupiravir therapy was associated with a significant reduction in all-cause mortality rate in this population compared with control (RR 0.31; 95% CI 0.12–0.80; P= 0.02; I 2: 0%) and in hospital admission (RR 0.79; 95% CI 0.66–0.94; P= 0.007; I 2: 47%). The use of molnupiravir was not associated with a significant reduction of all-cause mortality or hospital admission for subgroups including only patients with cardiovascular disease (RR 0.79; 95% CI 0.45–1.39; P= 0.41; I2: 0%) and diabetes (RR 0.85; 95% CI 0.51–1.42; P= 0.32; I2: 0%). Our results suggest that molnupiravir use might be considered in high-risk of severity disease, non-hospitalized patients.