Toxicological analysis of chronic exposure to polymeric nanocapsules with different coatings in Drosophila melanogaster.

Nanotechnology involves the utilization of nanomaterials, including polymeric nanocapsules (NCs) that are drug carriers. For modify drug release and stability, nanoformulations can feature different types of polymers as surface coatings: Polysorbate 80 (P80), Polyethylene glycol (PEG), Chitosan (CS) and Eudragit (EUD). Although nanoencapsulation aims to reduce side effects, these polymers can interact with living organisms, inducing events in the antioxidant system. Thus far, little has been described about the impacts of chronic exposure, with Drosophila melanogaster being an in vivo model for characterizing the toxicology of these polymers. This study analyzes the effects of chronic exposure to polymeric NCs with different coatings. Flies were exposed to 10, 50, 100, and 500 µL of NCP80, NCPEG, NCCS, or EUD. The survival rate, locomotor changes, oxidative stress markers, cell viability, and Nrf2 expression were evaluated. Between the coatings, NCPEG had minimal effects, as only 500 µL affected the levels of reactive species (RS) and the enzymatic activities of catalase (CAT) and glutathione S-transferase (GST) without reducing Nrf2 expression. However, NCEUD significantly impacted the total flies killed, RS, CAT, and Superoxide dismutase from 100 µL. In part, the toxicity mechanisms of these coatings can be explained by the imbalance of the antioxidant system. This research provided initial evidence on the chronic toxicology of these nanomaterials in D. melanogaster to clarify the nanosafety profile of these polymers in future nanoformulations. Further investigations are essential to characterize possible biochemical pathways involved in the toxicity of these polymeric coatings.

A Systematic Patent Review (2008-2023) for Treatment in Pregnancy.

INTRODUCTION: During pregnancy, the woman's body undergoes anatomical and physiological changes, making this period susceptible to maternal-fetal diseases and complications. The consequences of not treating pregnant women include premature birth, low birth weight fetuses, and postnatal behavior disorders. Developing new therapies can accelerate the discovery of safe and effective drugs, contributing to designing novel natural and synthetic products to treat complications the pregnancy. OBJECTIVE: This study aimed to carry out a patent review to identify and explore trends in innovation and therapeutic strategies for treating pregnant women. METHODS: The Espacenet and WIPO databases were used, with the inclusion criteria being the keywords "pregnancy and drug" and code A61k, from 2008 to 2023, and as exclusion were the access to the patent and focus on human pregnant women. RESULTS: After the final screening, 32 patents were selected, with strategies for the treatment of diseases in pregnant women. Of these, 20 patents are on preclinical studies on animals and 12 on pregnant women. It was observed that universities lead the ranking of applications (17/32), and China has the highest number of patents (18/32). Most findings contain herbal medicines and/or the association of natural extracts with synthetic drugs. CONCLUSION: From this perspective, new drug administration systems were also developed, which can be a promising source for obtaining new medicines for the treatment of pregnant women; however, research is still limited and shows a gap in stimulating the rapid development of safe drugs that improve the health of pregnant women.

Nanoencapsulated Curcumin: Enhanced Efficacy in Reversing Memory Loss in An Alzheimer Disease Model.

Investigating new drugs or formulations that target Alzheimer disease (AD) is critical for advancing therapeutic interventions. Therefore, this study aimed to assess the effectiveness of nanoencapsulated curcumin (NC Curc) in alleviating memory impairment, oxidative stress, and neuroinflammation in a validated AD model. Male Wistar rats were given bilateral intracerebroventricular injections of either saline or streptozotocin (STZ) (3 mg/3 µL/site) to establish the AD model (day 0). On day 22, daily oral administrations of curcumin (6 mg/kg), NC Curc (6 mg/kg), or a vehicle (unloaded NC) were initiated and continued for 14 days. NC Curc significantly reversed memory deficits in object recognition and inhibitory avoidance tests induced by STZ. Both formulations of curcumin attenuated elevated acetylcholinesterase activity caused by STZ. Importantly, NC Curc alone effectively mitigated STZ-induced oxidative stress. Additionally, NC Curc treatment normalized GFAP levels, suggesting a potential reduction in neuroinflammation in STZ-treated rats. Our findings indicate that NC Curc improves memory in an AD rat model, highlighting its enhanced therapeutic effects compared to unencapsulated curcumin. This research significantly contributes to understanding the therapeutic and neurorestorative potential of NC Curc in AD, particularly in reversing pathophysiological changes.

Bougainvillea glabra Choisy bracts extract in free and liposomal forms reduce hyperplasia induced by let-60gain-of-function in Caenorhabditis elegans.

In this study, we evaluated the toxicological and antiproliferative effects of B. glabra Choisy bract extract (BGCE) in its free and loaded into liposomes forms administered to C. elegans mutants with let-60 gain-of-function (gf). Our results demonstrated that the concentration up to 75 µg CAE/mL of BGCE was safe for the worms. Notably, we developed BGCE-loaded liposomes to extend the pharmacological window up to 100 µg CAE/mL without toxicity. In addition, the extract and liposomes reduced the number and area of the multivulva formed in let-60 gf mutants. There was also an increase in the apoptotic signaling in the germline cells and increased longevity mediated through DAF-16 nuclear translocation with GST-4 activation in the treated animals. Our findings demonstrated that the BGCE-loaded liposomes possess antitumoral effects due to the activation of the apoptotic signaling and DAF-16 nuclear translocation.

Evaluation of oxidative stress indicators as toxicity parameters after chronic exposure of Drosophila melanogaster to free curcumin and curcumin-loaded nanocapsules.

We investigated a possible toxic effect induced by chronic exposure to free curcumin and curcumin-loaded nanocapsules in Drosophila melanogaster, enabling safe applications. Flies of both sexes were divided into groups: control group; free curcumin at concentrations of 10, 30, 100, 300, 900, and 3000 µM; curcumin-loaded nanocapsules at concentrations of 10, 30, 100, and 300 µM. Initially, the diet consumption test was evaluated in flies exposed to different concentrations. During the 10-day treatment, the flies were evaluated for percentage survival. After the treatment, behaviors (geotaxis negative and open field), acetylcholinesterase activity (AChE), and oxidative stress parameters (reactive species (RS) and thiobarbituric acid reactive substances (TBARS) levels, Glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) enzymes activity, erythroid-derived nuclear factor 2 (Nrf2) immunoreactivity, and cellular metabolic capacity, were assessed. No significant difference in diet consumption, indicating that the flies equally consumed the different concentrations of free curcumin and the curcumin-loaded nanocapsules. Was observed that free curcumin and curcumin-loaded nanocapsules increased survival, locomotor and exploratory performance, decreased AChE activity, RS and TBARS levels, increased GST, SOD and CAT activity, Nrf2 and viable cells compared to the control. The chronic treatment did not cause toxicity, suggesting that nanoencapsulation of curcumin could be explored.

Development and In Vivo Assessment of 4-Phenyltellanyl-7-chloroquinoline-loaded Polymeric Nanocapsules in Alzheimer's Disease Models.

Alzheimer's disease (AD) is the most common form of dementia in older people, and available treatments are palliative and produce undesirable side effects. The 4-phenyltellanyl-7-chloroquinoline (TQ) is an organochalcogen compound studied due to its pharmacological properties, particularly its antioxidant potential. However, TQ possesses some drawbacks such as low aqueous solubility and high toxicity, thus warranting the search for tools that improve the safety and effectiveness of new compounds. Here, we developed and investigated the biological effects of TQ-loaded polymeric nanocapsules (NCTQ) in an AD model in transgenic Caenorhabditis elegans expressing human Aß1-42 in their body-wall muscles and Swiss mice injected with Aß25-35. The NCTQ displayed good physicochemical properties, including nanometer size and maximum encapsulation capacity. The treatment showed low toxicity, reduced Aß peptide-induced paralysis, and activated an endoplasmic reticulum chaperone in the C. elegans model. The Aß injection in mice caused memory impairment, which NCTQ mitigated by improving working, long-term, and aversive memory. Additionally, no changes in biochemical markers were evidenced in mice, demonstrating that there was no hepatotoxicity in the tested doses. Altogether, these findings provide insights into the neuroprotective effects of TQ and indicate that NCTQ is a promising candidate for AD treatment.

Clozapine-loaded nanocapsules improve antipsychotic activity in rats: building a sequential PopPK/PD model to discriminate nanocarriers in the preformulation step.

PURPOSE: We investigated the impact of nanoformulations on the dose-exposure-response relationship of clozapine (CZP), a low-solubility antipsychotic with serious adverse effects, using a popPK/PD approach. METHODS: We evaluated the pharmacokinetics and PK/PD profiles of three coated polymeric CZP-loaded nanocapsules functionalized with polysorbate 80 (NCP80), polyethylene glycol (NCPEG), and chitosan (NCCS). Data on in vitro CZP release by dialysis bag, plasma pharmacokinetic profiles in male Wistar rats (n = 7/group, 5 mg kg-1, i.v.), and percentage of head movements in a stereotyped model (n = 7/group, 5 mg kg-1, i.p.) were integrated using a sequential model building approach (MonolixSuiteTM-2020R1-Simulation Plus). RESULTS: A base popPK model developed with CZP solution data collected after the i.v. administration of CZP was expanded to describe the changes in drug distribution caused by nanoencapsulation. Two additional compartments were inserted into the NCP80 and NCPEG models, and a third compartment was included in the NCCS model. The nanoencapsulation showed a decrease in the central volume of distribution for NCCS (V1NCpop = 0.21 mL), while for FCZP, NCP80, and NCPEG, it was ~1 mL. The peripheral distribution volume was higher for the nanoencapsulated groups (19.1 and 129.45 mL for NCCS and NCP80, respectively) than for FCZP. The popPK/PD model showed a formulation-dependent plasma IC50, with 20-, 50-, and 80-fold reductions compared to the CZP solution (NCP80, NCPEG, and NCCS, respectively). CONCLUSION: Our model discriminates the coatings and describes the peculiar PK and PD behavior of nanoencapsulated CZP, especially NCCS, making it an exciting tool for evaluating the preclinical performance of nanoparticles.

Mechanical Properties of Protein-Based Hydrogels Derived from Binary Protein Mixtures-A Feasibility Study.

Hydrogels based on natural polymers such as proteins are considered biocompatible and, therefore, represent an interesting class of materials for application in the field of biomedicine and high-performance materials. However, there is a lack of understanding of the proteins which are able to form hydrogel networks by photoinduced dityrosine crosslinking as well as a profound knowledge of the formed network itself and the mechanisms which are responsible for the resulting mechanical properties of such protein-based hydrogels. In this study, casein, bovine serum albumin, α-amylase, and a hydrophobic elastin-like protein were used to prepare binary protein mixtures with defined concentration ratios. After polymerization, the mechanical properties of the resulting homopolymeric and copolymeric hydrogels were determined using rheological methods depending on the protein shares used. In additional uniaxial compression tests, the fracture strain was shown to be independent of the protein shares, while hydrogel toughness and compressive strength were increased for protein-based hydrogels containing casein.

Safety assessment of different unloaded polymeric nanocapsules in Caenorhabditis elegans.

Nano-sized drug delivery systems have been the subject of intense research in recent years because polymeric materials allow the absorption and release of active substances in a controlled manner. Despite the benefits, the safety of nanoparticulate systems is an aspect to be understood, particularly in vivo systems. Caenorhabditis elegans is a very useful alternative model for nanotoxicology and has been recently applied in this field. The aim of this study was to evaluate toxicological endpoints in C. elegans exposed to nanocapsules (NC) prepared with different coatings: polysorbate 80 (NCP80); polyethylene glycol (NCPEG), Eudragit® RS 100 (NCEUD) and chitosan (NCCS). Nanocapsules were prepared by nanoprecipitation method and showed acceptable physico-chemical characterization. Polyethylene glycol nanocapsules and chitosan nanocapsules increased worms lethality in a dose-dependent manner in acute exposure; polysorbate 80 nanocapsules, polyethylene glycol nanocpsules and chitonan nanocapsules also increased lethality following chronic exposure. Chitosan nanocapsules were the most toxic in all exposures, demonstrating toxicity even at low concentrations. Reproduction and body length were not affected by any of the nanocapsules exposures. The expression of superoxide dismutase showed that polysorbate 80 nanocapsules at the highest concentration slightly increased SOD-3::GFP expression. On the other hand, chitosan nanocapsules exposure blunted SOD-3 expression. This work demonstrates the toxicological differences between nanocapsule produced with different coatings and indicates higher safety for the use of eugragit nanocapsule in new formulations for future drug delivery and targeting systems.

Antiproliferative Cancer Cell and Fungicidal Effects of Yellow and Red Araçá (Psidium cattleianum Sabine) Fruit Extract.

Araçá is a native Brazil fruit, and has two morphological types, yellow and red; however, it is still little consumed by the population. Although there are few studies on the araçá fruit, some phytochemical propriety benefits have been described for this plant, such as antioxidant effects. To explore the benefits of araçá fruit, the physicochemical characteristics and in vitro toxicological effects of red and yellow araçá fruit were evaluated. In this work, the toxicity of araçá extracts in NIH/3T3 cell lines, the antiproliferative effects in cancer cell lines (C6, HT-29, and DU149), and the overall antifungal effects were evaluated. The irritant potential of araçá extracts was assessed by the HET-CAM test. The results demonstrated that the fruits are rich in fiber content and showed high phenols content. In addition, the araçá extracts had no present toxicity effects in cell lines; however, the red araçá extracts showed antiproliferative effects in HT-29 cancer cells at 50 mg/mL. The antifungal effects of araçá extract were promising in 23 isolates of Candida spp., and both araçá extracts showed no irritant effects. Therefore, this study demonstrated that red and yellow araçá fruit extract has promising biological and pharmacological effects that should be further explored.

Magnetic Resonance Imaging: Time-Dependent Wetting and Swelling Behavior of an Auxetic Hydrogel Based on Natural Polymers.

A time-dependent understanding of swelling characteristics and external stimuli behavior is crucial for the development and understanding of functional hydrogels. Magnetic resonance imaging (MRI) offers the opportunity to study three-dimensional (3D) soft materials nondestructively. This technique is already widely used as an image-based medical diagnostic tool and is applied here to evaluate complex structures of a hydrogel-a double network of chemically crosslinked casein enhanced with alginate-fabricated by 3D printing. When hydrogel disks immersed in four different liquid systems were analyzed, the material exhibited distinct system-dependent behavior characterized by rheological and mechanical measurements. Further material functionalization was achieved by macroscopic structuring of the hydrogel as an auxetic material based on a re-entrant honeycomb structure. MRI offers the advantage of monitoring overall changes in the area of the analyzed specimen and internal structural changes simultaneously. To assess the behavior of this complex structure, a series of short MRI measurements, each lasting 1.7 min, captured liquid diffusion and thus structural swelling behavior. A clear dependence of external and internal structural changes as a function of liquid properties causing these changes was observed. In conclusion, this approach might pave the way for prospective applications to monitor liquid diffusion into (e.g., vascularization) and swelling behavior of functional hydrogels.

The Importance of Skin Health Promotion for Children: Care with Makeup Use and Skin Cancer Prevention.

BACKGROUND: Numerous pathogenic complications affect the skin and are preventable, such as skin cancer, microbial diseases, dermal irritations, and anaphylaxis. In this context, the correct use of skin products, including sunscreens and child makeup, is important for promoting skin health and preventing adverse health conditions. OBJECTIVE: This study aimed to use educational and playful activities to promote skin health for students. METHODS: This project was development in a municipal elementary school (Rio Grande do Sul State, Brazil). The interventions were divided into three moments. In the first day, a questionnaire was applied to find out the students' previous knowledge about photoprotection. On the second day, an intervention lecture was held addressing issues related to photoprotection and the use of makeup. Finally, we played educational and ludic games and after, the questionnaire was reapplied. This was done to evaluate these actions' effectiveness regarding photoprotection and record their habits by applying a structured questionnaire at the beginning and end of the activities. RESULTS: Students received positively and interacted significantly during all activities performed. Regarding the impact of this study, we observed that ten times more students considered using sunscreen as something important at the end of the project, as only 8.16% of participants knew what skin cancer was at the beginning of the experiment. After the educational activities, this number rose to 72.37%, and 92.86% of girls reported wearing makeup, with more than half being expired or unlabeled and only 21.6% being appropriate for child use. CONCLUSION: The measures demonstrated effectively improve students' level of information regarding skin cancer prevention and indicated that inappropriate habits concerning makeup use in childhood are quite common, demonstrating the importance of educational interventions for children, since can improve your health.

In vivo and in vitro per se effect evaluation of Polycaprolactone and Eudragit® RS100-based nanoparticles.

Biodegradable polymeric nanocapsules (NC) present incredible characteristics as drug nanocarriers that optimize drug targeting. However, However, a more detailed isolated effect of polymer-based nanoparticles as drug carriers is required. This work aimed to evaluate the per se effect of blank-NC (NC-B) with different surface characteristics both in vitro and in vivo toxicity. NC1-B (Polysorbate 80 coated poly(ɛ-caprolactone) NC), NC2-B (polyethylene glycol 6000 coated poly(ɛ-caprolactone) NC), NC3-B (chitosan-coated poly(ɛ-caprolactone) NC) and NC4-B (Eudragit® RS100 NC) were prepared by nanoprecipitation method. Formulations were characterized by particle size, zeta potential, and pH. The in vitro cytotoxicity tests against tumor cell lines were performed (HepG2 and MCF-7). Antiviral activity was evaluated by MTT in Vero cells infected with HSV-1 (KOS strain). In vivo evaluation was performed in apomorphine-induced stereotypy in Wistar rats and locomotor activity distance, head movements, and rearing behavior were measured. NC1-B, NC2-B, NC3-B, and NC4-B had a diameter under 350 nm. The pH and zeta potential of formulations varied according to their coating. For in vitro evaluation of antitumor activity and antiviral activity, one-way ANOVA showed no significant differences in cell viability. In vivo tests showed low neurological effects. In conclusion, different surface characteristics of NC-B did not demonstrate toxicity against the evaluated cell lines HepG2 and MCF-7, antiviral effect against HSV-1, and the neurological effects in a stereotyping model were low and may be attributed to the per se effect of NC-B.

Changing mechanical properties of photopolymerized, dityrosine-crosslinked protein-based hydrogels.

Hydrogels based on renewable resources are a promising class of materials for future applications in pharmaceutics, drug delivery and personalized medicine. Thus, optional adjustments of mechanical properties such as swelling behavior, elasticity and network strength are desired. In this context, hydrogels based on the biological raw materials bovine serum albumin and casein were prepared by dityrosine-crosslinking of their tyrosine residues through visible light-induced photopolymerization. Changing the tyrosine accessibility by urea addition before photopolymerization increased the storage modulus of the hydrogels by 650% while simultaneously being more elastic. Furthermore, contributions of the buffer system composition, variation of protein concentration and storage medium towards mechanical properties of the hydrogel such as storage moduli, elasticity, fracture strain, compressive strength and relative weight swelling ratio are discussed. It could be shown, that changes in precursor solution and storage medium characteristics are crucial parameters towards tuning the mechanical properties of protein-based hydrogels.

Purification of a Hydrophobic Elastin-Like Protein Toward Scale-Suitable Production of Biomaterials.

Elastin-like proteins (ELPs) are polypeptides with potential applications as renewable bio-based high-performance polymers, which undergo a stimulus-responsive reversible phase transition. The ELP investigated in this manuscript-ELP[V2Y-45]-promises fascinating mechanical properties in biomaterial applications. Purification process scalability and purification performance are important factors for the evaluation of potential industrial-scale production of ELPs. Salt-induced precipitation, inverse transition cycling (ITC), and immobilized metal ion affinity chromatography (IMAC) were assessed as purification protocols for a polyhistidine-tagged hydrophobic ELP showing low-temperature transition behavior. IMAC achieved a purity of 86% and the lowest nucleic acid contamination of all processes. Metal ion leakage did not propagate chemical modifications and could be successfully removed through size-exclusion chromatography. The simplest approach using a high-salt precipitation resulted in a 60% higher target molecule yield compared to both other approaches, with the drawback of a lower purity of 60% and higher nucleic acid contamination. An additional ITC purification led to the highest purity of 88% and high nucleic acid removal. However, expensive temperature-dependent centrifugation steps are required and aggregation effects even at low temperatures have to be considered for the investigated ELP. Therefore, ITC and IMAC are promising downstream processes for biomedical applications with scale-dependent economical costs to be considered, while salt-induced precipitation may be a fast and simple alternative for large-scale bio-based polymer production.

Surface-functionalized curcumin-loaded polymeric nanocapsules could block apomorphine-induced behavioral changes in rats.

BACKGROUND: Surface functionalization enhances the properties and characteristics of polymeric nanocapsules (NCs) mainly due to the surface charge, surfactants, and polymer coating type. Curcumin (CUR) is a bioactive compound with several proven pharmacological properties and low bioavailability. This study aimed to develop anionic (poly-ɛ-caprolactone; PCL) and cationic (Eudragit® RS100 (EUD)) NCs prepared with sorbitan monostearate (Span 60®) or sorbitan monooleate (Span 80®), coated with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and optimized using 23 factorial analysis. Subsequently, the biological activity was evaluated. METHODS: A two-level, three-factor design (polymer, Span type, and TPGS concentration) was used. The biological effects of CUR-loaded TPGS-coated cationic and anionic NCs were assessed in apomorphine-induced stereotyped behavior in rats. RESULTS: The type of polymer (anionic or cationic) and Span® had a factorial influence on the physical and chemical characteristics of NCs according to the changes in TPGS concentrations. Both cationic and anionic CUR-NCs could block apomorphine-induced behavioral changes. CONCLUSIONS: The CUR-loaded TPGS-coated NCs proved to be a promising brain delivery system.

Relationship between toxicity and oxidative stress of the nanoencapsulated colchicine in a model of Drosophila melanogaster.

Drug repurposing allows searching for new biological targets, especially against emerging diseases such as Covid-19. Drug colchicine (COL) presents recognized anti-inflammatory action, while the nanotechnology purpose therapies with low doses, efficacy, and decrease the drug's side-effects. This study aims to evaluate the effects of COL and colchicine nanocapsules (NCCOL) on survival, LC50, activity locomotor, and oxidative stress parameters, elucidating the toxicity profile in acute and chronic exposure in Drosophila melanogaster. Three-day-old flies were investigated into groups: Control, 0.001, 0.0025, 0.005, and 0.010 mg/mL of COL or NCCOL. The survival rate, open field test, LC50, oxidative stress markers (reactive species (RS) production, thiobarbituric acid reactive substances), antioxidant enzyme activity (catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase), protein thiols, nonprotein thiols, acetylcholinesterase activity, and cell viability were measured. As a result, acute exposure to the COL decreases the number of crosses in the open field and increases CAT activity. NCCOL reduced RS levels, increased lipoperoxidation and SOD activity. Chronic exposure to the COL and NCCOL in high concentrations implied high mortality and enzymatic inhibition of the CAT and AChE, and only the COL caused locomotor damage in the open field test. Thus, NCCOL again reduced the formation of RS while COL increased. In this comparative study, NCCOL was less toxic to the antioxidant system than COL and showed notable involvement of oxidative stress as one of their toxicity mechanisms. Future studies are needed to elucidate all aspects of nanosafety related to the NCCOL.

Higher chances of survival to hospital admission after out-of-hospital cardiac arrest in patients with previously diagnosed heart disease.

AIM: This study aimed to determine whether patients suffering from out-of-hospital cardiac arrest (OHCA) with a pre-OHCA diagnosis of heart disease have higher survival chances than patients without such a diagnosis and to explore possible underlying mechanisms. METHODS: A retrospective cohort study in 3760 OHCA patients from the Netherlands (2010-2016) was performed. Information from emergency medical services, treating hospitals, general practitioner, resuscitation ECGs and civil registry was used to assess medical histories and the presence of pre-OHCA diagnosis of heart disease. We used multivariable regression analysis to calculate associations with survival to hospital admission or discharge, immediate causes of OHCA (acute myocardial infarction (AMI) vs non-AMI) and initial recorded rhythm. RESULTS: Overall, 48.1% of OHCA patients had pre-OHCA heart disease. These patients had higher odds to survive to hospital admission than patients without pre-OHCA heart disease (OR 1.25 (95%CI 1.05 to 1.47)), despite being older and more often having cardiovascular risk factors and some non-cardiac comorbidities. These patients also had higher odds of shockable initial rhythm (SIR) (OR 1.60 (1. 36 to 1.89)) and a lower odds of AMI as immediate cause of OHCA (OR 0.33 (0.25 to 0.42)). Their chances of survival to hospital discharge were not significantly larger (OR 1.16 (0.95 to 1.42)). CONCLUSION: Having pre-OHCA diagnosed heart disease is associated with better odds to survive to hospital admission, but not to hospital discharge. This is associated with higher odds of a SIR and in a subgroup with available diagnosis a lower proportion of AMI as immediate cause of OHCA.

Judicialization of health: lawsuits for access to medicines in Uruguaiana-RS / Judicialização da saúde: ações de acesso a medicamentos em Uruguaiana-RS

INTRODUCTION: In Brazil, the right to health has a constitutional and universal provision. However, the judicial route has been widely used to access health goods and services. OBJECTIVE: To analyze the lawsuits of medicines filed by citizens of a Brazilian municipality. METHODS: Quantitative and retrospective study evaluating 652 lawsuits filed in 2016 conducted in Uruguaiana, state of Rio Grande do Sul. The information was made available by the State Department of Health. RESULTS: 55.5% of lawsuits filed were related to drugs provided by the public health system Sistema Único de Saúde (SUS). 44.5% did not fit into the guidelines of the Brazilian Policy for Pharmaceutical Services. Most of the lawsuits were filed by women over 60 years old. Regarding the therapeutic classification, the most requested drugs were for the nervous system. The most described pathological condition according to the ICD-10 (International Classification of Diseases) was Diabetes Mellitus. CONCLUSION: These data corroborate the situation found in other parts of the country, demonstrating the need to reorganize the Pharmaceutical Service Policy to ensure universal and equitable access to medicines, as described in the Federal Constitution.

INTRODUÇÃO: No Brasil, o direito à saúde tem previsão constitucional e universal. No entanto, a via judicial tem sido muito usada para acessar bens e serviços de saúde. OBJETIVO: Analisar as demandas judiciais de medicamentos movidas por cidadãos de um município brasileiro. MÉTODOS: Realizou-se um estudo quantitativo e retrospectivo que avaliou 652 ações judiciais no ano de 2016 em Uruguaiana, estado do Rio Grande do Sul. As informações foram disponibilizadas pela Secretaria de Saúde estadual. RESULTADOS: 55,5% das demandas estavam relacionados a medicamentos fornecidos pelo Sistema Único de Saúde (SUS). 44,5% não se enquadravam em nenhum dos componentes da Política Nacional de Assistência Farmacêutica do Brasil. A maioria dos processos foram movidos por mulheres acima de 60 anos. Em relação à classificação terapêutica, os medicamentos mais solicitados foram para o Sistema Nervoso. A condição patológica mais descrita, segundo o CID-10 (Classificação Internacional de Doenças) foi Diabetes Mellitus. CONCLUSÃO: Tais dados corroboram com a situação encontrada em outras partes do país, demonstrando a necessidade de reorganização da Assistência Farmacêutica para garantir o acesso universal e equitativo aos medicamentos, conforme descrito na Constituição Federal.

Evaluation of curcumin-loaded polymeric nanocapsules with different coatings in chick embryo model: influence on angiogenesis, teratogenesis and oxidative stress.

BACKGROUND: Curcumin (CUR) is a bioactive compound with several proven pharmacological properties. However, the major limitation for therapeutic use of CUR is its low bioavailability. In this sense, an alternative to this question is the use of polymeric nanocapsules (NC) as drug/nutraceutical delivery systems. Thus, the aim of current study was to assess the effect of CUR-loaded NC and their different coatings in chick embryo model, evaluating angiogenic, teratogenic and oxidative stress parameters. METHODS: The physicochemical characterization of unloaded and loaded NC with different coatings: (U-NC (P80), U-NC (PEG), U-NC (EUD), U-NC (CS), CUR-NC (P80), CUR-NC (PEG), CUR-NC (EUD) and CUR-NC (CS)) were performed. After 9 days of incubation, eggs were treated (10 mL/kg eggs; via injection) with NC (unloaded and loaded with CUR) and CUR-solution. In sequence, hen's egg test-chorioallantoic membrane (HET-CAM), angiogenic assay, external abnormalities, weight of embryos and oxidative stress markers (TBARS, NPSH, ROS and CAT) were analyzed. RESULTS: CUR-NC (P80, PEG, EUD and CS) treatments caused antiangiogenic and non-teratogenic effects in chick embryo model. Still, CUR-NC (P80), CUR-NC (PEG), CUR-NC (EUD) and CUR-NC (CS) did not alter markers of oxidative stress (TBARS, NPSH, CAT) studied. Only CUR-NC (EUD) caused increase in ROS levels. CONCLUSION: Wherefore, these findings of present study represent a advance in research of drug/nutraceutical delivery systems.