The acronym ESKAPE includes six nosocomial pathogens that exhibit multidrug resistance and virulence: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. Persistent use of antibiotics has provoked the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) bacteria, which render even the most effective drugs ineffective. Extended spectrum β-lactamase (ESBL) and carbapenemase producing Gram negative bacteria have emerged as an important therapeutic challenge. Development of novel therapeutics to treat drug resistant infections, especially those caused by ESKAPE pathogens is the need of the hour. Alternative therapies such as use of antibiotics in combination or with adjuvants, bacteriophages, antimicrobial peptides, nanoparticles, and photodynamic light therapy are widely reported. Many reviews published till date describe these therapies with respect to the various agents used, their dosage details and mechanism of action against MDR pathogens but very few have focused specifically on ESKAPE. The objective of this review is to describe the alternative therapies reported to treat ESKAPE infections, their advantages and limitations, potential application in vivo, and status in clinical trials. The review further highlights the importance of a combinatorial approach, wherein two or more therapies are used in combination in order to overcome their individual limitations, additional studies on which are warranted, before translating them into clinical practice. These advances could possibly give an alternate solution or extend the lifetime of current antimicrobials.

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Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review.

Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways

Fluid phase equilibria

The family of bile acids includes a group of molecular species of acidic steroids with very peculiar physical-chemical and biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways that are controlled by mechanisms involving fine-tuning by the levels of certain bile acid species. Although their best-known role is their participation in the digestion and absorption of fat, they also play an important role in several other physiological processes. Thus, genetic abnormalities accounting for alterations in their synthesis, biotransformation and/or transport may result in severe alterations, even leading to lethal situations for which the sole therapeutic option may be liver transplantation. Moreover, the increased levels of bile acids reached during cholestatic liver diseases are known to induce oxidative stress and apoptosis, resulting in damage to the liver parenchyma and, eventually, extrahepatic tissues. When this occurs during pregnancy, the outcome of gestation may be challenged. In contrast, the physical-chemical and biological properties of these compounds have been used as the bases for the development of drugs and as pharmaceutical tools for the delivery of active agents.

Bile acids: Chemistry, physiology, and pathophysiology

A number of studies have shown a positive relationship between diets rich in soluble dietary fibres (SDF) such as β-glucan, pectin, guar gum and psyllium, and reduced serum cholesterol and thus a decreased risk of cardiovascular disease (CVD). Three major biological mechanisms have been proposed to explain the cholesterol-reducing effects of SDF: prevention of bile salt (BS) re-absorption from the small intestine leading to an excess faecal BS excretion; reduced glycemic response leading to lower insulin stimulation of hepatic cholesterol synthesis; and physiological effects of fermentation products of SDF, mainly propionate. Evidence for the latter mechanism is inconclusive, whereas in vivo, ex vivo and in vitro experiments suggest that BS micelles “bind” to SDF preventing their re-absorption. Whereas, glycemic responses to SDF have been studied extensively, the nature of interactions between bile salt micelles and SDF that lead to incomplete BS re-absorption are poorly defined. Three potential physicochemical mechanisms are proposed together with suggestions for in vitro experiments to test them.

Mechanisms underlying the cholesterol-lowering properties of soluble dietary fibre polysaccharides

the aim of the present study is to investigate the antioxidant potential of aqueous extracts of Menta x piperita from trás-os-montes by the DppH method, as well as to quantify the total phenolic compounds in the extracts by the Folin-ciocalteu method, probably responsible for the plant antioxidant properties. Additionally, the research work presented herein seeks to assess the effects of Menta x piperita through a series of in vitro cytotoxicity tests, using tetrahymena pyriformis as model organism. Viability will be evaluated by the colorimetric mtt assay. KEywORDS Menta x piperita; cytotoxicity; antioxidant activity; phenolic compounds

https://bdigital.ufp.pt/bitstream/10284/1286/1/344-354_FCS_06_-31.pdf

Actividade antioxidante e avaliação in vitro da citotoxicidade de extractos aquosos de folhas de mentha x piperita

Background Green tea is not only one of the most widely consumed beverages worldwide, but is also known for its health promoting and therapeutic effects. Green tea is cultivated in areas with high humidity and acidic soils in China, Indonesia and Japan. Those places have well-marked dry and rainy seasons. In opposite, Azores have a climate with constant average annual rainfall and, unlike eastern regions, relatively constant air humidity throughout the year. While a brand implemented on the Portuguese market, the quality of green tea produced in Azores must be guaranteed. Quality control measures based on phytochemical determination of the chemical composition and biological activities are needed in order to address whenever climate changes interferes significantly with composition and biological effects. Purpose Make the phytochemical characterization of various extracts of green tea leaves coming from Azores and evaluate the anti-cancer activities of the extracts in order to compare the obtained results with those of teas coming from eastern regions. Methods Phytochemical characterization (catechins, oxyaromatic acids, flavonols, alkaloids and theanine) and total catechins contents (TCC) was performed by using HPLC-DAD analysis, in infusions (5–7 min and 30 min), maceration and methanolic extracts of Camellia sinensis samples coming from Azores, Portugal. The antioxidant activity of extracts was measured by the DPPH assay and the total phenolics contents (TPC) were estimated using the Folin-Ciocalteu colorimetric method. The cytotoxic activity towards drug sensitive and multidrug-resistant leukemia cell lines was determined by the resazurin assay. Results The TCC was higher in methanolic extracts and lower in maceration, as epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) concentrations were significantly higher in methanolic extracts and were only residual in maceration extracts. Maceration extracts showed the highest content of gallic acid, indicating that methanol extracts contained more flavonols of higher molecular weight and/or that maceration may lead to the degalloylation of catechins. The amount of o-caffeoylquinic acid extracted was significantly higher in methanolic samples. Short-term extraction at high temperatures resulted in high amounts of neochlorogenic acid. The contents of glycosylated quercitin-3- d -galactoside and kaempferol-3-glucoside were small in maceration samples and high in methanolic samples. Caffeine was easily extracted by methanol (99%) compared with water, while extraction of the amino-acid l -theanine was unattainable with methanol. TPC values correlated linearly with DPPH• IC50, with infusion samples showing the best antioxidant capacities. The aqueous and the methanol/water extracts were active in multidrug-resistant and drug sensitive cancer cells. Conclusion Despite these climatic differences, the phytochemical characterization revealed that tea coming from the Azores compares well with those from China and Japan. In addition, tea can be produced without fungicides and pesticides to control pests that appear during rainy seasons. This allows the production of high-quality bioorganic tea. Aqueous and methanol/water extracts of the Azorean tea showed to be useful targeting sensitive and drug-resistant tumor cells.

https://bdigital.ufp.pt/bitstream/10284/10094/1/1-s2.0-S2667031320300014-main.pdf

Phytochemical characterization and biological activities of green tea (Camellia sinensis) produced in the Azores, Portugal

Development of a biotechnological process for the inhalational administration of a bacteriophage was pursued, using strategies of nanoencapsulation within lipid nanovesicles. As a proof-of-concept for the nanoencapsulation strategy, a bacteriophage with broad lytic spectrum was entrapped within W/O/W multiple nanoemulsions. Physicochemical characterization of the optimized bacteriophage-encasing nanovesicles encompassed determination of particle hydrodynamic size, size distribution and particle charge via DLS, surface morphology via CRYO-SEM, and thermal analysis via DSC, whereas antimicrobial activity of the nanoemulsions produced was assessed in vitro using several bacterial strains. The optimized nanosystems showed no phase separation and encompassed nanovesicles with an average size of ca. 114 nm and an average Zeta Potential of ca. -13 mV, which were maintained stable over a storage timeframe of ca. 3 months.

https://repositorium.sdum.uminho.pt/bitstream/1822/37177/1/document_3094_1.pdf

Design of a lipid nanovesicle system encapsulating bacteriophages integrated in a multiple emulsion formulation: a proof-of-concept

https://bdigital.ufp.pt/bitstream/10284/8327/1/Food%20Chemistry%202007.pdf

Changes in the pool of free fatty acids in ovine, bovine and caprine milk fats, effected by viable cells and cell-free extracts of Lactococcus lactis and Debaryomyces vanrijiae

Essential ultra-trace elements have an essential role in many physiological processes, regulating enzymes and metabolic pathways, being fundamental for growth, development, muscle and nerve function, normal cellular functioning, and synthesis of some hormones and connective tissue. Nevertheless, excessive levels of these elements can also lead to health problems, as neoplastic diseases. Another field of interest, that has been capturing researcher’s attention for several years, is the possibility of development of pharmacologically active compounds base in these ultra-trace minerals, as anticancer, anti-inflammatories, antidiabetic or antimicrobial agents. This article aims to review the main effects of ultra-trace elements in human health, namely selenium, chromium, molybdenum, cobalt, boron and iodine, focusing on the physiopathology and consequences of deficiency and/or excess of these elements. Also, it offers an overview of research information published in recent years concerning the use of these metals in compounds that show promising pharmacological activities. Carla Sousa, Carla Moutinho, Ana F. Vinha, Carla Matos 1 FP-ENAS ((Unidade de Investigação UFP em Energia, Ambiente e Saúde), CEBIMED (Centro de Estudos em Biomedicina), Universidade Fernando Pessoa), Porto,

Carla Moutinho

Papers

Actividade antioxidante e avaliação in vitro da citotoxicidade de extractos aquosos de folhas de mentha x piperita

Phytochemical characterization and biological activities of green tea (Camellia sinensis) produced in the Azores, Portugal

Design of a lipid nanovesicle system encapsulating bacteriophages integrated in a multiple emulsion formulation: a proof-of-concept

Changes in the pool of free fatty acids in ovine, bovine and caprine milk fats, effected by viable cells and cell-free extracts of Lactococcus lactis and Debaryomyces vanrijiae

Ultra-trace elements in human health: selenium, chromium, molybdenum, cobalt, boron and iodine