Utilização terapêutica das estatinas: indicações, novas perspetivas e efeitos laterais a curto e longo prazo

As doenças cardiovasculares são a principal causa de morte a nível mundial. Estas habitualmente estão associadas a um conjunto de condições que se designam por fatores de risco. Estes fatores podem ser modificáveis como o estilo de vida, a diabetes, a dislipidemia e hipertensão arterial ou não modificáveis como a hereditariedade, o sexo e a idade. Depois de terem sido descobertas as estatinas, no ano de 1978 estas passaram a ser os fármacos de eleição para o tratamento da dislipidemia quer na prevenção primária quer na prevenção secundária. As estatinas, atuam através da redução da HMG-CoA redutase, reduzindo a biossíntese do colesterol. São fármacos seguros, bem tolerados e muito eficazes, apresentando efeitos para além da redução dos níveis de colesterol, os chamados efeitos "pleiotrópicos". Estes efeitos incluem os efeitos anti-inflamatórios, antiproliferativos, antitrombóticos, imunomoduladores e ainda melhoria na doença de Alzheimer, na estabilidade da placa aterosclerótica, na função endotelial e no risco perioperatório. Têm sido efetuados estudos de maior detalhe que têm demonstrado que a atividade cardiovascular das estatinas, resulta de uma combinação destes efeitos. Tal como todos os outros fármacos existentes no mercado, as estatinas não são exceção e por isso, estão sujeitas a interações quando são usadas concomitantemente com outros fármacos e produzem efeitos colaterais a curto e longo prazo. Os efeitos colaterais a longo prazo mais importantes são a miopatia, a rabdomiólise e a insuficiência renal aguda. No entanto, é importante salientar que os benefícios associados às estatinas superam os riscos. As estatinas atualmente existentes no mercado são atorvastatina, fluvastatina, sinvastatina, rosuvastatina, pravastatina, lovastatina e a pitavastatina. Esta dissertação consiste numa revisão bibliográfica sobre as Estatinas focando as suas características farmacológicas e farmacocinéticas, os efeitos colaterais a curto e longo prazo e as possíveis perspetivas relativas aos efeitos pleiotrópicos.Cardiovascular diseases are the leading cause of death worldwide. These are usually associated with a set of conditions called risk factors. These factors may be referred to as modifiable, such as lifestyle and medicines, and non modifiable, such as genetic, gender and age. Statins were discovered in 1978 becoming the drugs of choice for the treatment of hypercholesterolemia in primary and secondary prevention. Statins act by inhibiting HMG-CoA reductase, leading to a reduction in cholesterol biosynthesis. They are safe, well tolerated and very effective drugs, with more effects than lowering cholesterol, called pleiotropic effects. These effects include anti-inflammatory, antiproliferative, antithrombotic and immunomodulatory effects showing further improvements in Alzheimer's disease, atherosclerotic plaque stability, endothelial function and perioperative risk. Studies have been done showing that the cardiovascular activity of statins results from a combination of these effects. Like all other drugs, statins are no exception presenting drug interaction and causing short and long term side effects. The more noted long-term side effects are myopathy, rhabdomyolysis and acute renal failure. However, it is important to mention that the benefits associated with statins outweigh the risks. The statins currently used include atorvastatin, fluvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin and pitavastatin. This paper consists is a bibliographic review about statins, pharmacological and pharmacokinetic properies, short and long term side effects and prospects for pleiotropic effects

Nanoencapsulation of bovine lactoferrin for oral hygiene applications

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Nanoencapsulation of bovine lactoferrin for food and biopharmaceutical applications

Lactoferrin has for long captured the interest of many researchers as a natural compound with a wide variety of uses. Lactoferrin is a monomeric, iron-binding 80 kDa glycoprotein, and appears to be the subfraction of whey with the best documented antiviral, antimicrobial, anticancer and immune modulating/enhancing effects. It belongs to the family of transferrin proteins, and serves to control iron levels in body fluids by sequestering and solubilizing ferric iron. In the present research effort, production of lactoferrin derivatives (starting from a purified commercial extract), encompassing full stabilization of its three-dimensional structure, has been attempted via nanoencapsulation within lipid nanovesicles, integrating a multiple water-in-oil-in-water emulsion. Long-term storage of the multiple nanoemulsions produced did not lead to leaching of protein, thus proving the effectiveness of the encapsulation procedure. Furthermore, lactoferrin nanovesicle derivatives prepared under optimal conditions were successfully employed at lab-scale antimicrobial trials.Financial support from Fundacao Ensino e Cultura Fernando Pessoa (FECFP, Porto, Portugal) and from Fundacao para a Ciencia e a Tecnologia (FCT, Lisbon, Portugal) as pluriannual funding, is gratefully acknowledged. Financial support to Victor M. Balcao, via an Invited Research Scientist fellowship (FAPESP Ref. No. 2011/51077-8) by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo, Brazil), is hereby gratefully acknowledged. The authors are also grateful to Dr. Madalena Vieira (affiliated with the IBB) for technical help

“The ark of rights”: development of a board game to empower older adults regarding their rights

There is an urgent need to ensure the rights of older adults. In particular, there is a lack of awareness of human rights by older adults themselves, for which intervention strategies should be developed. Due to the need for intervention at this level, a board game was created to empower older adults regarding their rights using a dynamic and interactive method. This article aims to describe the development stages of the board game “The Ark of Rights”® up to its pilot study. Its development followed three stages: A first phase to review the scientific literature and benchmarks on the rights of older persons, a second phase to define the game design and collect statements from older people for the game, and a third phase to test the game. The European Portuguese Validation of the System Usability Scale (SUS) was used to assess the latter phase. Approximately 200 older people contributed to the game’s contents (second phase), and 74 participated and positively evaluated the game’s usability and their satisfaction with its use (third phase). In summary, the game “The Ark of Rights” revealed itself to be a resource for empowering older adults regarding their rights. It also enables the identification of possible human rights violations among older adults and subsequent intervention.This research was funded by POISE/CIG 03 4436 FSE OO1051 under typology 3. 16, Financial and Technical Support to Non-Profit Civil Society Organizations, under Portugal 2020, specifically Priority Axis 3

Development of an inhalational therapeutical system based on bacteriophages to treat pharyngo-tonsillitis : a nanoencapsulation approach

Inflammatory diseases that occur in the pharynx and involving both the adenoids and tonsils are important not only for being very frequent, but also because they often require minor surgery for their resolution. These structures have immunological functions leading to production of antibodies, and work in the local immunity of the pharynx and protection of the entire body. The most common etiologic agent of sore throats is Streptococcus pyogenes, an important pathogen of the beta-hemolytic group A which causes streptococcal pharyngitis. The emergence of antibiotic-resistant bacterial strains and the poor penetration of chemical antibiotics in bacterial biofilms raise the need for safe and effective options of antimicrobial treatment. The application of bacteriophages (or cocktails therefrom) has been proposed as an alternative (or complement) to conventional chemical antibiotics, allowing the release of natural predators of bacteria directly on these biofilms. The major advantage of bacteriophage-based antibiotherapy relative to its conventional chemical counterpart is that bacteriophages replicate at the site of infection, being available in abundance where they are needed the most. When compared with chemical antibiotics, bacteriophages have other important advantages: (i) strong tissue permeability, (ii) bacteriophage concentration remains high at the focus of infection, continuously increasing with bacterial (host) presence, (iii) elimination of the focus of infection occurs only after eradication of the host bacterium, (iv) bacteriophages are fully compatible with antibiotics and may act synergistically, (v) they are specific against the target bacteria, (vi) have a superior ability to penetrate bacterial biofilms, inducing production of enzymes that hydrolyze the biofilm polymeric matrix, (vii) although bacteria can develop resistance to bacteriophages, isolation of new lytic bacteriophages is much simpler and cheaper than developing a new chemical antibiotic. In this research effort, development of a biotechnological process for the inhalational administration of a bacteriophage cocktail (endotoxin free) was pursued, using strategies of nanoencapsulation within lipid nanovesicles (as forms of protection for the bacteriophage against the immune system) to treat infectious pathologies such as pharyngo-tonsillitis caused by Streptococcus pyogenes. This method of targeting may have a high potential for the treatment of bacterial infections of the respiratory tract, since inhalation therapy is considered to be favorable to certain respiratory infections because the aerosol is delivered directly at the site of infection, accelerating the action of bacterial predators. Additionally, a smaller amount of bioactive substance is needed, thus preventing or reducing possible side effects. As a proof of concept for the nanoencapsulation strategy, and since there is not yet available a strictly lytic bacteriophage cocktail for Streptococcus pyogenes, a well-defined and characterized bacteriophage was utilized, viz. bacteriophage T4. Water-in-oil-in-water (W/O/W) multiple emulsions are nanosystems in which dispersions of small water droplets within larger oil droplets are themselves dispersed in a continuous aqueous phase. Due to their compartimentalized internal structure, multiple emulsions present important advantages over simple O/W emulsions for encapsulation of biomolecules, such as the ability to carry both polar and non-polar molecules, and a better control over releasing of therapeutic molecules. T4 bacteriophage was entrapped within W/O/W multiple nanoemulsions, aiming at mimicking the multifunctional design of biology, optimized with several lipid matrices, poloxamers and stabilizing layer compositions. Physicochemical characterization of the optimized bacteriophageencasing nanovesicle formulations encompassed determination of particle size, size distribution and particle charge, via Zeta potential analysis, surface morphology via CRYO-SEM, and thermal analysis via DSC

Protein hydrolysates from salmon heads and cape hake by-products: comparing enzymatic method with subcritical water extraction on bioactivity properties

Fish by-products can be converted into high-value-added products like fish protein hydrolysates (FPHs), which have high nutritional value and are rich in bioactive peptides with health benefits. This study aims to characterise FPHs derived from salmon heads (HPSs) and Cape hake trimmings (HPHs) using Alcalase for enzymatic hydrolysis and Subcritical Water Hydrolysis (SWH) as an alternative method. All hydrolysates demonstrated high protein content (70.4–88.7%), with the degree of hydrolysis (DH) ranging from 10.7 to 36.4%. The peptide profile of FPHs indicated the breakdown of proteins into small peptides. HPSs showed higher levels of glycine and proline, while HPHs had higher concentrations of glutamic acid, leucine, threonine, and phenylalanine. Similar elemental profiles were observed in both HPHs and HPSs, and the levels of Cd, Pb, and Hg were well below the legislated limits. Hydrolysates do not have a negative effect on cell metabolism and contribute to cell growth. HPSs and HPHs exhibited high 2,2′–azino-bis(3 ethylbenzthiazoline-6)-sulfonic acid (ABTS) radical scavenging activity, Cu2+ and Fe2+ chelating activities, and angiotensin-converting enzyme (ACE) inhibitory activity, with HPHs generally displaying higher activities. The α-amylase inhibition of both FPHs was relatively low. These results indicate that HPHs are a promising natural source of nutritional compounds and bioactive peptides, making them potential candidates for use as an ingredient in new food products or nutraceuticals. SWH at 250 °C is a viable alternative to enzymatic methods for producing FPHs from salmon heads with high antioxidant and chelating properties.info:eu-repo/semantics/publishedVersio

Population structure in Quercus suber L. revealed by nuclear microsatellite markers

Quercus suber L. is a sclerophyllous tree species native to the western Mediterranean, a region that is considered highly vulnerable to increased temperatures and severe dry conditions due to environmental changes. Understanding the population structure and demographics of Q. suber is essential in order to anticipate whether populations at greater risk and the species as a whole have the genetic background and reproductive dynamics to enable rapid adaptation. The genetic diversity of Q. suber has been subject to different studies using both chloroplast and nuclear data, but population structure patterns remain unclear. Here, we perform genetic analyses on Q. suber using 13 nuclear microsatellite markers, and analysed 17 distinct locations across the entire range of the species. Structure analyses revealed that Q. suber may contain three major genetic clusters that likely result from isolation in refugia combined with posterior admixture and putative introgression from other Quercus species. Our results show a more complex structure scenario than previously inferred for Q. suber using nuclear markers and suggest that different southern populations contain high levels of genetic variation that may contribute to the resilience of Q. suber in a context of environmental change and adaptive pressureinfo:eu-repo/semantics/publishedVersio

Inflammatory and Cardiometabolic Risk on Obesity: Role of Environmental Xenoestrogens

Some chemicals used in consumer products or manufacturing (eg, plastics, pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect immune responses and have recently emerged as a new risk factors for obesity and cardiovascular disease. However, the extent and impact on health of chronic exposure of the general population to XEs are still unknown.info:eu-repo/semantics/publishedVersio