CONSUMISMO E SUPERENDIVIDAMENTO

Há muito sabe-se que as necessidades humanas são finitas, mas os desejos infinitos; a necessidade é saciada com a apropriação ou consumo de algo preemente e indispensável à vida humana. È mister ponderar que o indivíduo já nasce com elas, e saciá-las consiste no que há de mais intrínseco e primitivo no ser humano. Não se pode viver sem saciar a fome, o sono, a sede, etc. Como o homem é um ser social, agrega ainda necessidades outras como moradia, transporte, vestuário, et

O HISTÓRICO DA DEFESA DO CONSUMIDOR NO BRASIL E NA ARGENTINA.

O presente trabalho visa demonstrar o panorama da evolução histórico-jurídica dos sistemas de defesa do consumidor no Brasil e na Argentina. As Revoluções Industrial e Francesa modificaram sobremaneira a forma dos indivíduos da sociedade consumirem os bens da vida, bem como, modificaram os instrumentos jurídicos (principalmente os contratos) que passaram a ter que amoldar-se a uma realidade de produção e consumo em massa. Neste sentido, resta clara a importância da consolidação de um sistema legal protetivo ao vulnerável no mercado de consumo

Contrato de Empréstimo Bancário ao Consumidor

SUMÁRIO: Introdução. Contratos de empréstimo. Mútuo Feneratício. Microssistema de consumo e incidência do CDC. Disciplina jurídica do CDC. Fenômeno do superendividamento. Conclusão. INTRODUÇÃO Na sociedade contemporânea, as relações jurídicas contratuais privadas apresentam-se cada vez mais céleres, impessoais e derivadas da produção em série; o contrato não mais é negócio jurídico amplamente discutido entre as partes e fruto da convergência igualitária das vontades. O contrato na contemporaneidade apresentam-se, normalmente, em forma de formulário padrão, onde são ofertados os mesmos produtos e serviços a qualquer um que se disponha a adquirí-los mediante pagamento; pouco importando a eventual presença de uma desigualdade de forças no vínculo contratual que se forma, em virtude de ser um dos contratantes um vulnerável

Pyrazole-Enriched Cationic Nanoparticles Induced Early- and Late-Stage Apoptosis in Neuroblastoma Cells at Sub-Micromolar Concentrations

Neuroblastoma (NB) is a severe form of tumor occurring mainly in young children and originating from nerve cells found in the abdomen or next to the spine. NB needs more effective and safer treatments, as the chance of survival against the aggressive form of this disease are very small. Moreover, when current treatments are successful, they are often responsible for unpleasant health problems which compromise the future and life of surviving children. As reported, cationic macromolecules have previously been found to be active against bacteria as membrane disruptors by interacting with the negative constituents of the surface of cancer cells, analogously inducing depolarization and permeabilization, provoking lethal damage to the cytoplasmic membrane, and cause loss of cytoplasmic content and consequently, cell death. Here, aiming to develop new curative options for counteracting NB cells, pyrazole-loaded cationic nanoparticles (NPs) (BBB4-G4K and CB1H-P7 NPs), recently reported as antibacterial agents, were assayed against IMR 32 and SHSY 5Y NB cell lines. Particularly, while BBB4-G4K NPs demonstrated low cytotoxicity against both NB cell lines, CB1H-P7 NPs were remarkably cytotoxic against both IMR 32 and SHSY 5Y cells (IC50 = 0.43–0.54 µM), causing both early-stage (66–85%) and late-stage apoptosis (52–65%). Interestingly, in the nano-formulation of CB1H using P7 NPs, the anticancer effects of CB1H and P7 were increased by 54–57 and 2.5–4-times, respectively against IMR 32 cells, and by 53–61 and 1.3–2 times against SHSY 5Y cells. Additionally, based on the IC50 values, CB1H-P7 was also 1-12-fold more potent than fenretinide, an experimental retinoid derivative in a phase III clinical trial, with remarkable antineoplastic and chemopreventive properties. Collectively, due to these results and their good selectivity for cancer cells (selectivity indices = 2.8–3.3), CB1H-P7 NPs represent an excellent template material for developing new treatment options against NB

Mini-Tablets: A Valid Strategy to Combine Efficacy and Safety in Pediatrics

open6In the treatment of pediatric diseases, mass-produced dosage forms are often not suitable for children. Commercially available medicines are commonly manipulated and mixed with food by caregivers at home, or extemporaneous medications are routinely compounded in the hospital pharmacies to treat hospitalized children. Despite considerable efforts by regulatory agencies, the pediatric population is still exposed to questionable and potentially harmful practices. When designing medicines for children, the ability to fine-tune the dosage while ensuring the safety of the ingredients is of paramount importance. For these purposes solid formulations may represent a valid alternative to liquid formulations for their simpler formula and more stability, and, to overcome the problem of swelling ability, mini-tablets could be a practicable option. This review deals with the different approaches that may be applied to develop mini-tablets intended for pediatrics with a focus on the safety of excipients. Alongside the conventional method of compression, 3D printing appeared particularly appealing, as it allows to reduce the number of ingredients and to avoid both the mixing of powders and intermediate steps such as granulation. Therefore, this technique could be well adaptable to the daily galenic preparations of a hospital pharmacy, thus leading to a reduction of the common practice of off-label preparations.openZuccari, Guendalina; Alfei, Silvana; Marimpietri, Danilo; Iurilli, Valentina; Barabino, Paola; Marchitto, LeonardoZuccari, Guendalina; Alfei, Silvana; Marimpietri, Danilo; Iurilli, Valentina; Barabino, Paola; Marchitto, Leonard

Preparation and Characterization of Amorphous Solid Dispersions for the Solubilization of Fenretinide

Fenretinide (4-HPR), a retinoid derivative, has shown high antitumor activity, a low toxicological profile, and no induction of resistance. Despite these favorable features, the variability in oral absorption due to its low solubility combined with the high hepatic first pass effect strongly reduce clinical outcomes. To overcome the solubility and dissolution challenges of poorly water-soluble 4-HPR, we prepared a solid dispersion of the drug (4-HPR-P5) using a hydrophilic copolymer (P5) previously synthesized by our team as the solubilizing agent. The molecularly dispersed drug was obtained by antisolvent co-precipitation, an easy and up-scalable technique. A higher drug apparent solubility (1134-fold increase) and a markedly faster dissolution were obtained. In water, the colloidal dispersion showed a mean hydrodynamic diameter of 249 nm and positive zeta potential (+41.3 mV), confirming the suitability of the formulation for intravenous administration. The solid nanoparticles were also characterized by a high drug payload (37%), as was also evidenced by a chemometric-assisted Fourier transform infrared spectroscopy (FTIR) investigation. The 4-HPR-P5 exhibited antiproliferative activity, with IC50 values of 1.25 and 1.93 µM on IMR-32 and SH-SY5Y neuroblastoma cells, respectively. Our data confirmed that the 4-HPR-P5 formulation developed herein was able to increase drug apparent aqueous solubility and provide an extended release over time, thus suggesting that it represents an efficient approach to improve 4-HPR bioavailability

Potent and Broad-Spectrum Bactericidal Activity of a Nanotechnologically Manipulated Novel Pyrazole

: The antimicrobial potency of the pyrazole nucleus is widely reported these days, and pyrazole derivatives represent excellent candidates for meeting the worldwide need for new antimicrobial compounds against multidrug-resistant (MDR) bacteria. Consequently, 3-(4-chlorophenyl)-5-(4-nitrophenylamino)-1H-pyrazole-4-carbonitrile (CR232), recently reported as a weak antiproliferative agent, was considered to this end. To overcome the CR232 water solubility issue and allow for the determination of reliable minimum inhibitory concentration values (MICs), we initially prepared water-soluble and clinically applicable CR232-loaded nanoparticles (CR232-G5K NPs), as previously reported. Here, CR232-G5K NPs have been tested on several clinically isolates of Gram-positive and Gram-negative species, including MDR strains. While for CR232 MICs 65 128 \ub5g/mL (376.8 \ub5M) were obtained, very low MICs (0.36-2.89 \ub5M) were observed for CR232-G5K NPs against all of the considered isolates, including colistin-resistant isolates of MDR Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemases (KPCs)-producing K. pneumoniae (0.72 \ub5M). Additionally, in time-kill experiments, CR232-G5K NPs displayed a rapid bactericidal activity with no significant regrowth after 24 h on all isolates tested, regardless of their difficult-to-treat resistance. Conjecturing a clinical use of CR232-G5K NPs, cytotoxicity experiments on human keratinocytes were performed, determining very favorable selectivity indices. Collectively, due to its physicochemical and biological properties, CR232-G5K NPs could represent a new potent weapon to treat infections sustained by broad spectrum MDR bacteria