Antimicrobial activity of essential oils against biofilms formed in dental acrylic resin: a systematic review of in vitro studies.

This study aimed to answer the question formulated according to the PICO strategy: 'Which essential oils show antimicrobial activity against biofilms formed on dental acrylic resin?' composed by population (dental acrylic resin), intervention (application of essential oils), comparison (denture cleansers, antifungal drugs, chlorhexidine, and oral mouthwashes), and outcome (antibiofilm activity). In vitro experimental studies evaluating the activity of EOs on biofilm formed on acrylic resin were included. PRISMA guidelines were followed, and the search was performed in the PubMed, Science Direct, Embase, and Lilacs databases and in the gray literature using Google Scholar and ProQuest in December 2023. A manual search of the reference lists of the included primary studies was performed. Of the 1467 articles identified, 37 were selected for full-text reading and 12 were included. Twelve EOs were evaluated, of which 11 showed activity against Candida spp., 3 against Staphylococcus aureus, and 1 against Pseudomonas aeruginosa. The EOs of Cymbopogon citratus, Cinnamomum zeylanicum, and Cymbopogon nardus showed higher action than chlorhexidine, C. nardus higher than Listerine, C. citratus higher than nystatin, and Melaleuca alternifolia higher than fluconazole and nystatin. However, chlorhexidine was more effective than Lippia sidoides and Salvia officinalis, sodium hypochlorite was more effective than L. sidoides, nystatin was more effective than Zingiber officinale, Amphotericin B more effective than Eucalyptus globulus and M. alternifolia. In conclusion, the EOs of C. zeylanicum, C. citratus, C. nardus, and M. alternifolia showed antimicrobial activity to reduce biofilm on dental acrylic resin.

Denture stomatitis: Treatment with antimicrobial drugs or antifungal gels? A systematic review of clinical trials.

STATEMENT OF PROBLEM: Gel formulations containing antimicrobials are a potential alternative for the development of new medicines for the treatment of denture stomatitis (DS). However, whether they are more effective than antifungal drugs is unclear. PURPOSE: The purpose of this systematic review was to identify whether gels formulated with antimicrobial substances are more effective and biocompatible for the treatment of DS than antifungal drugs. MATERIAL AND METHODS: This systematic review was structured according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022379510). Searches were performed in the PubMed, Lilacs, Web of Science, Scopus, Embase, and Google Scholar databases in November 2022. Randomized and nonrandomized clinical trials comparing the efficacy of experimental gels and conventional antifungals in the treatment of DS were included. RESULTS: Gels formulated with Zataria multiflora essential oil and clove and cinnamon extracts showed higher antimicrobial efficacy compared with miconazole and clotrimazole. Formulations containing Uncaria tomentosa, Punica granatum, and propolis extract showed similar efficacy to nystatin and miconazole. Two formulations containing P. granatum were less effective than nystatin and miconazole. Gels of Z. multiflora and miconazole induced adverse effects including burning, itching, nausea, and vomiting. The included studies did not evaluate the biocompatibility of the gels. CONCLUSIONS: Gels formulated with natural antimicrobials such as Z. multiflora, U. tomentosa, P. granatum, propolis, and clove and cinnamon showed higher or similar antimicrobial efficacy to conventional antifungals in the treatment of DS. The biocompatibility of experimental gels based on natural agents should be evaluated.

Phytoconstituents and Ergosterol Biosynthesis-Targeting Antimicrobial Activity of Nutmeg (Myristica fragans Houtt.) against Phytopathogens.

In recent years, nutmeg (Myristica fragans Houtt.) has attracted considerable attention in the field of phytochemistry due to its diverse array of bioactive compounds. However, the potential application of nutmeg as a biorational for crop protection has been insufficiently explored. This study investigated the constituents of a nutmeg hydroethanolic extract via gas chromatography-mass spectrometry and vibrational spectroscopy. The research explored the extract's activity against phytopathogenic fungi and oomycetes, elucidating its mechanism of action. The phytochemical profile revealed fatty acids (including tetradecanoic acid, 9-octadecenoic acid, n-hexadecanoic acid, dodecanoic acid, and octadecanoic acid), methoxyeugenol, and elemicin as the main constituents. Previously unreported phytochemicals included veratone, gelsevirine, and montanine. Significant radial growth inhibition of mycelia was observed against Botrytis cinerea, Colletotrichum acutatum, Diplodia corticola, Phytophthora cinnamomi, and especially against Fusarium culmorum. Mode of action investigation, involving Saccharomyces cerevisiae labeled positively with propidium iodide, and a mutant strain affected in ERG6, encoding sterol C-24 methyltransferase, suggested that the extract induces a necrotic type of death and targets ergosterol biosynthesis. The evidence presented underscores the potential of nutmeg as a source of new antimicrobial agents, showing particular promise against F. culmorum.

Empowering frail older adults: multicomponent elastic-band exercises and BCAA supplementation unleash physical health and preserve haematological biomarkers.

The effectiveness of Branched Chain Amino Acids (BCAAs) supplementation on enhancing exercise performance in both young and older adults remains a topic of debate. Recent research suggests that BCAAs combined with regular exercise might have an impact on human erythropoiesis, blood dynamics, and iron homeostasis. Given the increasing longevity of the global population, it is crucial to investigate the potential benefits of BCAA supplementation and regular exercise as non-pharmacological interventions for improving the overall health of frail older adults. To assess the influence of a 40-week multicomponent exercise intervention (MEP) combined BCCA supplementation on the haematological indicators of frail older adults (83-93 years old) residing in nursing homes. A prospective, naturalistic, controlled clinical trial employing an intervention-washout-intervention was conducted for this purpose. The study included four experimental groups: MEP plus BCAA supplementation (MEP + BCAA, n = 8), MEP only (n = 7), BCAA supplementation only (n = 7), and control group non exercising (CG, n = 13). Fried's physical frailty (PF) protocol was employed to stratify the participants. Additionally, the assessment included the evaluation of nutritional status, comorbidities, and anthropometric measurements. Among the several haematological markers examined, only mean cellular Haemoglobin Concentration (MCH) [F = 4.09; p < 0.03] and Mean Cell haemoglobin Concentration (MCHC) [F = 10, 323; p < 0,0001] showed significant effects of time group. Our findings demonstrate that a long-term intervention with BCAA plus MEP did not lead to significant alterations in the haematological profile. An 8-week withdrawal from interventions did not affect the frailty status in the MEP and MEP + BCAA groups, whereas the control group exhibited an increase in PF status. The findings, demonstrating the potential pro-immune effect and maintenance of MCH and MCHC levels, highlight the relevance of incorporating exercise and nutritional strategies to promote healthy aging. This study contributes to the achievement of the United Nations Sustainable Development Goals 3 (good health and well-being) and 10 (reduced Inequalities) for all.

Glucose-Functionalized Silver Nanoparticles as a Potential New Therapy Agent Targeting Hormone-Resistant Prostate Cancer cells.

Purpose: Silver nanoparticles (AgNPs) have shown great potential as anticancer agents, namely in therapies' resistant forms of cancer. The progression of prostate cancer (PCa) to resistant forms of the disease (castration-resistant PCa, CRPC) is associated with poor prognosis and life quality, with current limited therapeutic options. CRPC is characterized by a high glucose consumption, which poses as an opportunity to direct AgNPs to these cancer cells. Thus, this study explores the effect of glucose functionalization of AgNPs in PCa and CRPC cell lines (LNCaP, Du-145 and PC-3). Methods: AgNPs were synthesized, further functionalized, and their physical and chemical composition was characterized both in water and in culture medium, through UV-visible spectrum, dynamic light scattering (DLS), transmission electron microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR). Their effect was assessed in the cell lines regarding AgNPs' entering pathway, cellular proliferation capacity, ROS production, mitochondrial membrane depolarization, cell cycle analysis and apoptosis evaluation. Results: AgNPs displayed an average size of 61nm and moderate monodispersity with a slight increase after functionalization, and a round shape. These characteristics remained stable when redispersed in culture medium. Both AgNPs and G-AgNPs were cytotoxic only to CRPC cells and not to hormone-sensitive ones and their effect was higher after functionalization showing the potential of glucose to favor AgNPs' uptake by cancer cells. Entering through endocytosis and being encapsulated in lysosomes, the NPs increased the ROS, inducing mitochondrial damage, and arresting cell cycle in S Phase, therefore blocking proliferation, and inducing apoptosis. Conclusion: The nanoparticles synthesized in the present study revealed good characteristics and stability for administration to cancer cells. Their uptake through endocytosis leads to promising cytotoxic effects towards CRPC cells, revealing the potential of G-AgNPs as a future therapeutic approach to improve the management of patients with PCa resistant to hormone therapy or metastatic disease.

Effect of a 40-weeks multicomponent exercise program and branched chain amino acids supplementation on functional fitness and mental health in frail older persons.

BACKGROUND: The ageing process implies several physiological and psychological changes that hence affect the general health, mood states, and quality of life of older persons. Exercise and adequate nutrition are renowned non-pharmacological strategies that significantly delay and alleviate the adverse consequences of the ageing process. This study aimed to evaluate the effects of branched-chain amino acid (BCAA) supplementation and a multicomponent exercise program (ME) on the physical frailty and mood states of older persons. METHODS: 35 participants (women and men; 83 ± 3 years old) from residential care homes were submitted to a 40-week exercise-washout-retraining intervention (16 weeks of the elastic band based exercise and/or supplementation, 8 weeks of washout, and 16 weeks of multicomponent exercise and/or resupplementing), with or without BCAA supplementation. The experimental groups were: (i) ME plus BCAA supplementation (ME+BCAA); (ii) ME; (iii) BCAA supplementation (BCAA), and (iv) control group (CG). Fried's phenotype was used to assess frailty prevalence. Geriatric Depression Scale (GDS), Profile of Mood State (POMS), Mini-Mental State Examination (MMSE), were used to access mental health and cognition. The Short Physical Performance Battery (SPPB) was used to access functional capacity. Salivary testosterone levels (ST) were also determined to access the anabolic effects of the intervention. RESULTS: Exercise was effective in improving functional capacity and prevented the increase in frailty that occurred in the non-exercising CG, where the frailty scores increased over time (p < 0.01). BCAAs supplement alone had no impact on functional fitness, but in a short time (16 weeks) contributed to diminishing frailty and combined with exercise may have the potential to reduce the effect of a detraining period on functional capacity. Salivary testosterone levels correlated with handgrip strength and could be a useful indicator of susceptibility to frailty. No effects were found for mood states, cognition, and depression. CONCLUSION: This study showed that a long-term exercise program, independent of being multicomponent or strength elastic band-based, was effective in improving functional capacity and prevented an increase in frailty in frail and pre-frail older persons living in residential care homes.

Physical Exercise: A Versatile Anti-Inflammatory Tool Involved in the Control of Hypothalamic Satiety Signaling.

The hypothalamus plays a critical role in the control of food consumption and energy expenditure. Fatty diets can elicit an inflammatory response in specific hypothalamic cells, including astrocytes, tanycytes, and microglia, disrupting anorexigenic signals in region-specific hypothalamic neurons, contributing to overeating and body weight gain. In this study, we present an update regarding the knowledge of the effects of physical exercise on inflammatory signaling and circuits to control hunger in the hypothalamus in obesity conditions. To try to understand changes in the hypothalamus, we review the use of magnetic resonance/anorexigenic hormone analysis in humans, as well as in animal models to explore the physiological and molecular mechanism by which exercise modulates satiety signals, such as the central anti-inflammatory response, myokine delivery from skeletal muscle, and others. The accumulation of scientific evidence in recent years allows us to understand that exercise contributes to weight control, and it is managed by mechanisms that go far beyond "burning calories."

A Review on the Biological Activity of Camellia Species.

Medicinal plants have been used since antiquity to cure illnesses and injuries. In the last few decades, natural compounds extracted from plants have garnered the attention of scientists and the Camellia species are no exception. Several species and cultivars are widespread in Asia, namely in China, Japan, Vietnam and India, being also identified in western countries like Portugal. Tea and oil are the most valuable and appreciated Camellia subproducts extracted from Camellia sinensis and Camellia oleifera, respectively. The economic impact of these species has boosted the search for additional information about the Camellia genus. Many studies can be found in the literature reporting the health benefits of several Camellia species, namely C. sinensis, C. oleifera and Camellia japonica. These species have been highlighted as possessing antimicrobial (antibacterial, antifungal, antiviral) and antitumoral activity and as being a huge source of polyphenols such as the catechins. Particularly, epicatechin (EC), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and specially epigallocatechin-3-gallate (EGCG), the major polyphenols of green tea. This paper presents a detailed review of Camellia species' antioxidant properties and biological activity.

Effect of Training-Detraining Phases of Multicomponent Exercises and BCAA Supplementation on Inflammatory Markers and Albumin Levels in Frail Older Persons.

Nowadays, it is accepted that the regular practice of exercise and branched-chain amino acids supplementation (BCAAs) can benefit the immune responses in older persons, prevent the occurrence of physical frailty (PF), cognitive decline, and aging-related comorbidities. However, the impact of their combination (as non-pharmacological interventions) in albumin and the inflammatory markers is not fully understood. Therefore, we investigated the effect of a 40-week multifactorial intervention [MIP, multicomponent exercise (ME) associated or not with BCAAs] on plasma levels of inflammatory markers and albumin in frail older persons (≥75 years old) living at residential care homes (RCH). This study consisted of a prospective, naturalistic, controlled clinical trial with four arms of multifactorial and experimental (interventions-wahshout-interventions) design. The intervention groups were ME + BCAAs (n = 8), ME (n = 7), BCAAs (n = 7), and control group (n = 13). Lower limb muscle-strength, cognitive profile, and PF tests were concomitantly evaluated with plasma levels of albumin, anti- and pro-inflammatory cytokines [Interleukin-10 (IL-10) and Tumor Necrosis Factor-alpha (TNF-α) respectively], TNF-α/IL-10 ratio, and myeloperoxidase (MPO) activity at four different time-points: Baseline (T1), after 16 weeks of multifactorial intervention (T2), then after a subsequent 8 weeks washout period (T3) and finally, after an additional 16 weeks of multifactorial intervention (T4). Improvement of cognitive profile and muscle strength-related albumin levels, as well as reduction in the TNF-α levels were found particularly in ME plus BCAAs group. No significant variations were observed over time for TNF-α/IL-10 ratio or MPO activity. Overall, the study showed that MIP triggered slight alterations in the inflammatory and physical function of the frail older participants, which could provide independence and higher quality of life for this population.

Taurine supplementation reduces myeloperoxidase and matrix-metalloproteinase-9 levels and improves the effects of exercise in cognition and physical fitness in older women.

Immunosenescence contributes to cognitive impairment and neurodegeneration, and those conditions could be attenuated by non-pharmacological anti-inflammatory strategies, such as exercise and supplementation with the amino acid taurine. Since taurine body content decreases with aging, we investigated the effects of supplementation (alone and combined with exercise) on oxidative stress, extracellular matrix degradation, white blood cells, neurotrophins, cognition and physical fitness of elderly women. Forty-eight women (83.58 ± 6.98 years) were enrolled into exercise training only (EO: n = 13), taurine supplementation (TS: n = 12), exercise training + taurine supplementation (ETTS: n = 11), and control group (CG: n = 12). All interventions lasted 14 weeks. Exercise was applied twice a week, and taurine was given once a day (1.5 g). Data collection occurred before and after interventions with the determination of myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) levels, and white blood cell counts (WBC). Montreal cognitive assessment (MoCA) and physical fitness tests were also evaluated. Concentration of MPO and MMP-9 decreased after intervention in TS (p < 0.05). No effect of time or time × group was observed for WBC parameters; however, univariate analysis showed a significant decrease in lymphocytes for TS, while an increase in monocytes occurred in the CG (p < 0.05). MoCA scores decreased over time in the CG (p < 0.05). Improvements in physical fitness occurred in ETTS (better agility and aerobic capacity), mostly likely due to exercise and boosted by taurine supplementation. No changes in BDNF levels were observed (p > 0.05), while NGF concentration were undetectable in almost subjects. Exercise together with taurine supplementation appears to be a valuable strategy to enhance health-related outcomes in older persons.

Spirituality and quality of life in older adults: a path analysis model.

BACKGROUND: Study older adults' quality of life is becoming increasingly important in the assessment, quality improvement and allocation of health and social care service. The purpose of this study was to enhance knowledge on the relationship between modifiable (psychological variables) and non-modifiable variables (sociodemographic), and quality of life in elderly, regarding psychological and social variables in Portuguese context. METHODS: This is a cross-sectional study, including 604 older adults from general community. 63.6% of the sample was composed by female gender with a mean age of 71.6(SD = 4.81). Participants completed the following instruments: Barthel Index to assess functionality; Satisfaction with Social Support Scale to assess social support; The Spiritual and Religious Attitudes in Dealing with Illness to assess spirituality and Short Form Health Survey 36, to assess mental and physical quality of life. RESULTS: A path analysis model was performed where the presence of a chronic disease, age and functionality has a direct effect on physical quality of life and spirituality had a direct effect on mental quality of life. Social support mediated the relationship between functionality and mental quality of life, and in turn, functionality mediated the relationship between age and physical quality of life. CONCLUSIONS: Results reinforce the effect of age and chronic disease as non-modifiable variables as well as functionality, spirituality and satisfaction with social support as modifiable variables, in the quality of life of older people. Social support, health and education programs in the community should be promoted in order to improve quality of life in this population. Strategies to promote functionality and enhance the social support network, especially in the elder with chronic illness, should be a priority.

Chair-based exercise programs in institutionalized older women: Salivary steroid hormones, disabilities and frailty changes.

PURPOSE: Many people experience aging-related losses in different physical domains, which leads to a condition often called physical frailty (PF). The aim of this study was to analyse the effects of two different, 28-weeks, class chair-exercise protocols on salivary steroid hormones (SH), PF, and functional disabilities (FD) in frail older women. METHODS: A sample of older frail individuals (n = 60, 817.84 years) participated in the study and were divided into three groups: chair elastic-band muscle strength exercises (CSE), n = 20), chair-multimodal exercise (CME, n = 21) and a control non-exercise group (CGne, n = 19). Both exercise programs consisted of 45 min of supervised chair-based exercise group classes, carried out 3 times/week. CME participants performed a progressive training using walking, mobility and body weight resistance exercises. The CSE participants exercised using an elastic-band system of progressive exercises. Both CSE and CME followed a circuit training protocol. The controls did not change their usual lifestyle. The indicators of PF, FD and SH concentrations were analyzed before and after the intervention. RESULTS: Both exercise programs diminished the PF status showing significant time and time versus treatment interactions (p < .01). An increase in the CME group, between baseline and 14-weeks, and in the CSE group, after 28 weeks, for Testosterone concentrations was observed (p < .01). Dehydroepiandrosterone (DHEA) increased after 28-weeks in the CME group and decreased in the CGne after the same period (p < .05). Both exercise programs decreased the negative scores of several FD domains, specially fear of falling that showed significant effects with time (p < .01), and time vs intervention (p < .05). CONCLUSION: Both chair-exercise based programs were effective in stimulating positive changes in physical health and in steroid hormone responses, especially in DHEA. The control group did show a negative trend towards an increased PF status and decreased levels of SH. It is crucial for public health to identify the main factors associated with Functional Disability and Physical Frailty that underlie the development of new methods for complementary therapies, such as the use of low doses of hormonal supplementation combined with long-term exercise interventions.

1,8-Cineole blocks voltage-gated L-type calcium channels in tracheal smooth muscle.

1,8-Cineole is a cyclic monoterpenoid used in folk medicine for treatment of numerous respiratory diseases and other infections. 1,8-Cineole has anti-inflammatory, antioxidant, and myorelaxant effects, as well as low toxicity. In the present study, the effects of 1,8-cineole on contractility and voltage-gated calcium channels (VGCC) in tracheal smooth muscle were investigated. Intact and dissociated tracheal smooth muscle were used for muscle contraction and patch-clamp recordings, respectively. In experiments involving muscle contraction, 1,8-cineole potentiated contractions at low concentrations and relaxed contractions induced by isotonic K+ at high concentrations. AMTB (a TRPM8 channel blocker) reduced the potentiation induced by 1,8-cineole while indomethacin (a COX inhibitor) did not block this effect. In dissociated myocytes, 1,8-cineole partially blocked Ba2+ currents through VGCC in a concentration-dependent manner. 1,8-Cineole shifted the steady-state activation and inactivation curves to the left and also reduced the current decay time constant. In conclusion, 1,8-cineole has a dual effect on tracheal smooth muscle contraction resulting in a biphasic effect. Our data suggest that the potentiation effect is mediated by activation of TRPM8 channels and the relaxation effect is mediated by the blockage of L-type VGCC.

The Quadruple Helix-Based Innovation Model of Reference Sites for Active and Healthy Ageing in Europe: The Ageing@Coimbra Case Study.

Challenges posed by demographic changes and population aging are key priorities for the Horizon 2020 Program of the European Commission. Aligned with the vision of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), the development, exchange, and large-scale adoption of innovative good practices is a key element of the responses required to ensure all European citizens remain as active and healthy as possible as they age. Urged by the need of developing scalable disruptive innovation across Europe, the European Commission and the EIP on AHA created the Reference Sites; local coalition of partners that develop good practices to support AHA. Ageing@Coimbra is an example of how this can be achieved at a regional level. The consortium comprises over 70 institutions that develop innovative practices to support AHA in Portugal. Ageing@Coimbra partners support a regional network of stakeholders that build a holistic ecosystem in health and social care, taking into consideration the specificities of the territories, living environments and cultural resources (2,243,934 inhabitants, 530,423 aged 65 or plus live in the Centre Region of Portugal). Good practices in reducing the burden of brain diseases that affect cognition and memory impairment in older people and tackling social isolation in urban and rural areas are among the top priorities of Ageing@Coimbra. Profiting from the collaborative work of academia, business companies, civil society, and authorities, the quadruple helix of Ageing@Coimbra supports: early diagnosis of frailty and disease; care and cure; and active, assisted, and independent living. This paper describes, as a Community Case Study, the creation of a Reference Site of the EIP on AHA, Ageing@Coimbra, and its impact in Portugal. This Reference Site can motivate other regions to develop innovative formulas to federate stakeholders and networks, building consortia at regional level. This growing movement, across Europe, is inspired by the quadruple helix concept and by the replication of innovative good practices; creating new Reference Sites for the benefit of Citizens.

Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women.

Immunosenescence contribute to increase the blood-brain barrier (BBB) permeability, leading cognitive impairment and neurodegeneration. Thus, we investigated the anti-inflammatory effect of exercise and taurine supplementation on peripheral markers of BBB, inflammation, and cognition of elderly women. Forty-eight elderly women (age, 83.58 ± 6.9 years) participated in the study, and were allocated into combined exercise training (CET: n = 13), taurine supplementation (TAU: n = 12), exercise training associated with taurine (CET+TAU: n = 11), or control (CG: n = 12) groups. Exercise was applied twice a week (multi-modal exercise). Taurine ingestion was 1.5 g., once a day. Participants were evaluated before and after 14-weeks of intervention. Plasma levels of interleukin (IL)-1ß, IL-1ra, IL-6, IL-10, IL-17, tumor necrosis factor alpha (TNF-α), and serum concentration of S100ß and neuron specific enolase (NSE) were determined. The mini mental state examination (MMSE) was also applied. Concentrations of S100ß were maintained in all intervention groups, while a subtle increase in the CG was found. NSE levels increased only in TAU group (p < 0.05). CET reduced TNF-α, IL-6, and IL-1ß/IL-1ra, IL-6/IL10, and TNF-α/IL-10 ratios (p < 0.05). TAU decreased the IL-1ß/IL-1ra ratio (p < 0.05). MMSE score increased only in the CET+TAU group (p < 0.05). Multiple regression analysis showed that there was a trend for changes in IL-1ß and the Charlson Comorbidity Index to be independently associated with changes in S100ß. Exercise and taurine decreased inflammation, and maintained the BBB integrity in elderly women. Exercise emerged as an important tool to improve brain health even when started at advanced ages.

Metabolic flux profiling of MDCK cells during growth and canine adenovirus vector production.

Canine adenovirus vector type 2 (CAV2) represents an alternative to human adenovirus vectors for certain gene therapy applications, particularly neurodegenerative diseases. However, more efficient production processes, assisted by a greater understanding of the effect of infection on producer cells, are required. Combining [1,2-(13)C]glucose and [U-(13)C]glutamine, we apply for the first time (13)C-Metabolic flux analysis ((13)C-MFA) to study E1-transformed Madin-Darby Canine Kidney (MDCK) cells metabolism during growth and CAV2 production. MDCK cells displayed a marked glycolytic and ammoniagenic metabolism, and (13)C data revealed a large fraction of glutamine-derived labelling in TCA cycle intermediates, emphasizing the role of glutamine anaplerosis. (13)C-MFA demonstrated the importance of pyruvate cycling in balancing glycolytic and TCA cycle activities, as well as occurrence of reductive alphaketoglutarate (AKG) carboxylation. By turn, CAV2 infection significantly upregulated fluxes through most central metabolism, including glycolysis, pentose-phosphate pathway, glutamine anaplerosis and, more prominently, reductive AKG carboxylation and cytosolic acetyl-coenzyme A formation, suggestive of increased lipogenesis. Based on these results, we suggest culture supplementation strategies to stimulate nucleic acid and lipid biosynthesis for improved canine adenoviral vector production.

Terapêutica Fotodinâmica com metil-aminolevulinato no tratamento de lesões refractárias de Micose Fungóide: resposta clínica e histológica mantida em dois doentes.

According to the guidelines proposed by the National Comprehensive Cancer Network, early-stage Mycosis Fungoides (MF) should be treated with skin-directed therapies such as topical steroids or retinoids, topical chemotherapy (carmustin and nitrogen mustard), photochemotherapy, and superficial radiotherapy. Patients with refractory lesions to these therapeutic options are particularly challenging. Photodynamic Therapy (PDT) has been approved to treat cutaneous neoplastic and pre-neoplastic lesions such as superficial basal cell carcinoma, Bowen disease and actinic keratosis. Recently, several small studies have demonstrated the efficacy of PDT with methyl-aminolaevulinate (MAL) in the treatment of early-stage MF. We report two patients diagnosed with IA and IB MF, previously treated with conventional treatments (topical steroids and photochemotherapy) with short-term recurrence that were treated with PDT with MAL with complete and maintained response for one year. Our findings confirm that PDT with MAL can be one more palliative option in the treatment of early-stage MF, especially in pauci-lesional disease or in lesions resistant or inaccessible to conventional therapies.

Dietary unsaturated fatty acids differently affect catecholamine handling by adrenal chromaffin cells.

Catecholamines (CA) play an important role in cardiovascular (CDV) disease risk. Namely, noradrenaline (NA) levels positively correlate whereas adrenaline (AD) levels negatively correlate with obesity and/or CDV disease. Western diets, which are tipically rich in Ω-6 fatty acids (FAs) and deficient in Ω-3 FAs, may contribute to the development of obesity, type 2 diabetes and/or coronary artery disease. Taking this into consideration and the fact that our group has already described that saturated FAs affect catecholamine handling by adrenal chromaffin cells, this work aimed to investigate the effect of unsaturated FAs upon catecholamine handling in the same model. Our results showed that chronic exposure to unsaturated FAs differently modulated CA cellular content and release, regardless of both FA series and number of carbon atoms. Namely, the Ω-6 arachidonic and linoleic acids, based on their effect on CA release and cellular content, seemed to impair NA and AD vesicular transport, whereas γ-linolenic acid selectively impaired AD synthesis and release. Within the Ω-9 FAs, oleic acid was devoid of effect, and elaidic acid behaved similarly to γ-linolenic acid. Eicosapentaenoic and docosahexaenoic acids (Ω-3 series) impaired the synthesis and release of both NA and AD. These results deserve attention and future development, namely, in what concerns the mechanisms involved and correlative effects in vivo.

Etiological agents and antimicrobial susceptibility in hospitalized children with acute pyelonephritis.

INTRODUCTION: Antibiotic resistance driven by antibiotic use remains a major public health and professional concern. Our aim was to know the local prevalence of uropathogens and their antimicrobial susceptibility profile in acute pyelonephritis. MATERIAL AND METHODS: A prospective study of patients admitted in a level III Pediatric Department ward with acute pyelonephritis from 1994 to 2012 was performed in Northern Portugal. Etiological agents and their antimicrobial sensitivity profile were evaluated in four timed periods (G1: 1994-97; G2: 2002; G3: 2007; G4: 2012). RESULTS: We evaluated 581 patients, 66% female with median age 22 months. Escherichia coli was the leading uropathogen and its prevalence remained stable during the last 18 years. It showed an increased sensitivity to amoxicillin-clavulanate from 71% in G1 to 81.5% in G4 (p = 0.001) and a decreased resistance rate from 8.7% in G1 to 2.8% in G4 (p = 0.008). Its sensitivity to 2nd and 3rd generation cephalosporin was more than 90% (p = ns) and more than 95% to nitrofurantoin (p = ns). Resistance rate of cotrimoxazole increased from 22% to 26% (p = 0.008). DISCUSSION: Escherichia coli remains the main uropathogen responsible for acute pyelonephritis, reason why its antimicrobial sensitivity profile will determine the empirical therapeutic choice. CONCLUSIONS: Amoxicillin-clavulanate remains a good first-line choice for empirical treatment of acute pyelonephritis in our inpatient health care.

Introdução: A resistência aos antimicrobianos, provocada pela utilização de antibióticos continua a ser um importante problema de saúde pública e uma preocupação para os profissionais de saúde. O nosso objetivo foi conhecer a prevalência local dos uropatógenos e o seu perfil de suscetibilidade aos antimicrobiannos na pielonefrite aguda. Material e Métodos: Estudo prospetivo nas crianças internadas por pielonefrite aguda no internamento de Pediatria de um hospital do norte de Portugal entre 1994-2012. Os agentes etiológicos e o seu perfil de sensibilidade aos antimicrobianos foram avaliados em quatro períodos de tempo (G1: 1994-1997, G2: 2002; G3: 2007; G4: 2012). Resultados: Avaliámos 581 doentes, 66% do sexo feminino, com idade mediana de 22 meses. A Escherichia coli foi o principal uropatógeno e a sua prevalência manteve-se estável durante os últimos 18 anos. Verificou-se um aumento da sensibilidade à amoxicilina/ácido clavulânico de 71% no G1 para 81,5% no G4 (p = 0,001) e uma diminuição da taxa de resistência de 8,7% no G1 para 2,8% G4 (p = 0,008). A sua sensibilidade às cefalosporinas de segunda e terceira geração e nitrofurantoína foi superior a 90% (p = ns). A taxa de resistência ao cotrimoxazol aumentou de 22 % para 26 % (p = 0,008). Discussão: A Escherichia coli continua a ser o uropatogénio mais frequente responsável por pielonefrite aguda, motivo pelo qual o seu perfil de sensibilidade aos antimicrobianos determina a escolha da antibioticoterapia empírica. Conclusões: A amoxicilina/ácido clavulânico mantém-se como escolha de primeira linha para o tratamento empírico da pielonefrite aguda em regime de internamento.

Natural bioactive compounds from winery by-products as health promoters: a review.

The relevance of food composition for human health has increased consumers' interest in the consumption of fruits and vegetables, as well as foods enriched in bioactive compounds and nutraceuticals. This fact has led to a growing attention of suppliers on reuse of agro-industrial wastes rich in healthy plant ingredients. On this matter, grape has been pointed out as a rich source of bioactive compounds. Currently, up to 210 million tons of grapes (Vitis vinifera L.) are produced annually, being the 15% of the produced grapes addressed to the wine-making industry. This socio-economic activity generates a large amount of solid waste (up to 30%, w/w of the material used). Winery wastes include biodegradable solids namely stems, skins, and seeds. Bioactive compounds from winery by-products have disclosed interesting health promoting activities both in vitro and in vivo. This is a comprehensive review on the phytochemicals present in winery by-products, extraction techniques, industrial uses, and biological activities demonstrated by their bioactive compounds concerning potential for human health.