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STUDY QUESTION: Are there any associations of dietary patterns with semen quality, reproductive hormone levels, and testicular volume, as markers of testicular function? SUMMARY ANSWER: These results suggest that traditional Mediterranean diets may have a positive impact on male reproductive potential. WHAT IS KNOWN ALREADY: The Mediterranean diet has been related to lower risk of multiple chronic diseases, but its effects on reproduction potential are unclear. STUDY DESIGN, SIZE, DURATION: Cross-sectional sample of 215 male university students recruited from October 2010 to November 2011 in Murcia Region (Spain). PARTICIPANTS/MATERIALS, SETTING, METHODS: Two hundred and nine healthy men aged 18-23 years were finally included in this analysis. Diet was assessed using a validated food frequency questionnaire, and dietary patterns were identified by factor analysis. Linear regression was used to analyze the relation between diet patterns with semen quality parameters, reproductive hormone levels and testicular volume adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: We identified two dietary patterns: a Mediterranean (characterized by high intakes of vegetables, fruits and seafood) and a Western pattern (characterized by high intakes of processed meats, French fries and snacks). The Mediterranean pattern was positively associated with total sperm count (P, trend = 0.04). The Western pattern was positively related to the percentage of morphologically normal sperm (P, trend = 0.008). We found an inverse association between adherence to the Western pattern and sperm concentration among overweight or obese men (P, trend = 0.04). LIMITATIONS, REASONS FOR CAUTION: As with all cross-sectional studies, causal inference is limited. However, participants were blinded to the study outcomes thus reducing the potential influenced their report of diet. Although we adjusted for a large number of known and suspected confounders, we cannot exclude the possibility of residual confounding or chance findings. WIDER IMPLICATIONS OF THE FINDINGS: This study was carried out on healthy and young men, so it is difficult to predict whether and how the observed differences in semen quality translate into reproductive success for men in couples trying to conceive. These results suggest that traditional Mediterranean diets may have a positive impact on male reproductive potential.
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Dieta Mediterrânea , Dieta Ocidental , Contagem de Espermatozoides , Espermatozoides/citologia , Adolescente , Forma Celular/fisiologia , Estudos Transversais , Humanos , Masculino , Análise do Sêmen , Adulto JovemRESUMO
OBJECTIVE: Animal models have suggested that anogenital distance (AGD) at birth reflects androgen levels during in utero development and predicts adult AGD. A recent study showed an association between perineal length and androgen levels in men, suggesting that serum testosterone levels in adulthood will depend on factors involved during the fetal period. The aim of this study is to assess the relationship between AGD measures and reproductive hormone levels in women. DESIGN: Cross-sectional study conducted between February and November 2011. SETTING: University-affiliated fertility clinics. POPULATION: 100 young college students. METHODS: Physical and gynaecological examinations were conducted on university students. All participants provided a blood sample for determination of reproductive hormones and completed an epidemiological questionnaire on lifestyles and gynaecological history. We used multiple linear regression analysis to examine the associations between perineal length measurements [anus-fourchette (AGDAF ) and anus-clitoris (AGDAC )] and reproductive hormone levels. MAIN OUTCOME MEASURES: Anogenital distance measurements and reproductive hormone levels. RESULTS: In the multiple linear regression analyses, AGDAF was positively associated with serum testosterone levels. Serum testosterone increased 0.06 ng/ml (95%CI 0.01, 0.10; P = 0.02) for each 1-cm increase in AGDAF . None of the measurements was associated with other reproductive hormones. CONCLUSIONS: Anogenital distance may predict normal reproductive development in women, and may be a new tool of potential clinical interest to evaluate ovarian function. Our results suggest that serum testosterone levels in adulthood may depend on factors operating in the prenatal period.
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Canal Anal/anatomia & histologia , Fertilidade , Folículo Ovariano/fisiologia , Períneo/anatomia & histologia , Testosterona/sangue , Adolescente , Adulto , Estudos Transversais , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Genitália Feminina/anatomia & histologia , Humanos , Hormônio Luteinizante/sangue , Exame Físico , Valor Preditivo dos Testes , Prolactina/sangue , Inquéritos e QuestionáriosRESUMO
PURPOSE: Preclinical studies suggest a potential protective effect of oleuropein in osteoporosis, and one of the proposed mechanisms is the modulation of the oxidative stress. Oleuropein bioavailability and its effect on antioxidant status in pre- and postmenopausal women are unknown. The aim of the present study was to investigate the oral bioavailability of an olive leaf extract rich in oleuropein (40 %) and its effect on antioxidant status in postmenopausal women compared to premenopausal women. METHODS: Premenopausal (n = 8) and postmenopausal women (n = 8) received 250 mg of olive leaf extract, blood samples (t = 0, 1, 2, 3, 4, 6, 8, 12, 16 and 24 h) were taken, and 24-h urine divided into five fractions was collected. Olive-leaf-extract-derived metabolites were analyzed in plasma and urine by HPLC-ESI-QTOF and UPLC-ESI-QqQ, and pharmacokinetics parameters were determined. Ferric reducing antioxidant ability and malondialdehyde levels were measured in plasma. RESULTS: Plasma levels of hydroxytyrosol glucuronide, hydroxytyrosol sulfate, oleuropein aglycon glucuronide and oleuropein aglycon derivative 1 were higher in postmenopausal women. MDA levels were significantly decreased (32%) in postmenopausal women and inversely correlated with hydroxytyrosol sulfate levels. Postmenopausal women excreted less sulfated metabolites in urine than premenopausal women. CONCLUSIONS: Our results suggest that postmenopausal women could be a target population for the intake of olive phenolics in order to prevent age-related and oxidative stress-related processes such as osteoporosis.
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Antioxidantes/metabolismo , Iridoides/farmacocinética , Olea/química , Fenóis/farmacocinética , Extratos Vegetais/farmacocinética , Folhas de Planta/química , Adolescente , Adulto , Idoso , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Glucosídeos Iridoides , Iridoides/administração & dosagem , Iridoides/sangue , Iridoides/urina , Malondialdeído/sangue , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Fenóis/sangue , Fenóis/urina , Extratos Vegetais/administração & dosagem , Pós-Menopausa/sangue , Pós-Menopausa/urina , Pré-Menopausa/sangue , Pré-Menopausa/urina , Adulto JovemRESUMO
Biosimilars are products similar to a biological already authorized and no longer protected by a patent. As the biological product, they contain a biological substance produced by or derived from a living organism. Alike with generics, biosimilars are potential tool to ensure savings for health systems. The current lack of market penetration of biosimilars may be seen by national authorities as a lost opportunity in terms of cost- containment. The objective of this paper is therefore to analyze the current situation in Belgium and to identify potential measures to stimulate biosimilar uptake in Belgium through an analysis of the experience in five European countries: France, Germany, The Netherlands, Spain and Sweden. This international comparison was performed using a two steps analysis: a structured review of the literature followed by a validation from experts in each country. Potential incentives and constraints were identified, i.e., prescription quotas/target, clinical guidelines, primary substitution, reference price system, fixed payment and public tendering. However, the literature reviewed provided little evaluation of the effectiveness of these policies in terms of biosimilar uptake or potential savings. The impact of these policies on biosimilar related savings is currently based on expectation and assumptions. Such kind of studies is therefore essential in the future.
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Medicamentos Biossimilares/economia , Bélgica , Indústria Farmacêutica/economia , Indústria Farmacêutica/tendências , Medicamentos Genéricos , Europa (Continente) , HumanosRESUMO
Many physical, social, and psychological changes occur during aging that raise the risk of developing chronic diseases, frailty, and dependency. These changes adversely affect the gut microbiota, a phenomenon known as microbe-aging. Those microbiota alterations are, in turn, associated with the development of age-related diseases. The gut microbiota is highly responsive to lifestyle and dietary changes, displaying a flexibility that also provides anactionable tool by which healthy aging can be promoted. This review covers, firstly, the main lifestyle and socioeconomic factors that modify the gut microbiota composition and function during healthy or unhealthy aging and, secondly, the advances being made in defining and promoting healthy aging, including microbiome-informed artificial intelligence tools, personalized dietary patterns, and food probiotic systems.
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Dieta , Microbioma Gastrointestinal , Envelhecimento Saudável , Estilo de Vida , Humanos , Microbioma Gastrointestinal/fisiologia , Probióticos , EnvelhecimentoRESUMO
Resveratrol (RSV) was known to be metabolised by the gut microbiota to dihydroresveratrol, lunularin (LUNU), and (or) 3,4'-dihydroxy-trans-stilbene (DHST). We describe here for the first time that LUNU can be further dehydroxylated, but only at the 3-position, to yield 4-hydroxydibenzyl, a novel metabolite found in human urine after RSV intake in 41 out of 59 healthy participants. In contrast, DHST was not further dehydroxylated, and thus, 4-hydroxy-trans-stilbene was not detected as a gut microbial metabolite of RSV. Faecal in vitro incubations confirmed the in vivo results.
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Microbioma Gastrointestinal , Estilbenos , Antioxidantes , Fezes , Humanos , Resveratrol , Estilbenos/farmacologiaRESUMO
BACKGROUND: Health-related quality of life (HRQoL) of patients with X-linked hypophosphatemia (XLH) is lower than that of both the general population and the patients with other chronic diseases, mainly due to diagnostic delay, treatment difficulties, poor psychosocial support, and problems with social integration. Early diagnosis and optimal treatment are paramount to control the disease in patients with XLH, avoid complications, and maintain or improve their HRQoL. We, therefore, analyzed the HRQoL of pediatric and adult patients with XLH treated with conventional therapy in Spain. RESULTS: We used several versions of the EuroQol-5 dimensions (EQ-5D) instrument according to the age of patients with XLH. Then we compared the HRQoL of patients to that of the general Spanish population. Children with XLH (n = 21) had moderate problems in walking about (61.9%), washing or dressing themselves (9.52%), and performing their usual activities (33.33%). They also felt moderate pain or discomfort (61.9%) and were moderately anxious or depressed (23.81%). Adults with XLH (n = 29) had lower HRQoL, with problems in walking (93%, with 3.45% unable to walk independently), some level of pain (86%, with 3.45% experiencing extreme pain), problems with their usual activities (80%) and self-care (> 50%), and reported symptoms of anxiety and/or depression (65%). There were important differences with the general Spanish population. CONCLUSIONS: XLH impacts negatively on physical functioning and HRQoL of patients. In Spanish patients with XLH, the HRQoL was reduced despite conventional treatment, clearly indicating the need to improve the therapeutic approach to this disorder.
X-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affectingX-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affecting bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.
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Raquitismo Hipofosfatêmico Familiar , Adulto , Criança , Diagnóstico Tardio , Humanos , Dor , Qualidade de Vida/psicologia , EspanhaRESUMO
PURPOSE: The high mortality index due to sepsis and the lack of an effective treatment requires the search for new compounds that can serve as therapy for this disease. Resveratrol, a well-known anti-inflammatory natural compound, might be a good candidate for the treatment of sepsis. The aim of this work was to study the effects of oral administration of resveratrol, before and after sepsis initiation, on inflammation markers in a murine model of endotoxin-induced sepsis. METHODS: Sprague-Dawley male rats were treated with resveratrol the 3 days prior to LPS administration and 45 min later. Hematological parameters, TNF-α, IL-1ß and CINC-1, FRAP and TBARS levels were determined. Resveratrol and resveratrol-derived metabolites profile in plasma was compared after oral and intraperitoneal administration. RESULTS: Oral treatment with resveratrol had no apparent systemic protective effects. However, resveratrol reduced the levels of lipid peroxidation in the small intestine and colon. Importantly, the administration of LPS caused a decrease in resveratrol absorption. When resveratrol bioavailability after i.p. administration was compared to that observed after oral administration, a different profile of resveratrol metabolites was found in plasma. CONCLUSION: These results highlight the importance of studying the bioavailability of the assayed compounds in the experimental models used to be able to choose the best route of administration depending on the target organ and to determine which compounds or derived metabolites are effective treating the studied disease.
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Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Sepse/tratamento farmacológico , Estilbenos/farmacologia , Administração Oral , Animais , Antioxidantes/metabolismo , Cromatografia Líquida , Endotoxinas/toxicidade , Inflamação/induzido quimicamente , Interleucina-1beta/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Resveratrol , Espectrometria de Massas em Tandem , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: A centralised approach to health technology assessment (HTA) may facilitate optimal use of HTA resources. A regional approach may increase the chances of local implementation of recommendations. This study aimed to compare assessment procedures in England (centralised HTA approach) with Spain (regional HTA approach) discussing key challenges and opportunities from both approaches. METHODS: We compared technology assessments of anticancer medicines in the two jurisdictions from 2008 to 2015. To assess the implementation of HTA recommendations, we assessed trends in medicine usage using regression methods. We used IQVIA data, from 2011 to 2016, for a sample of 11 medicines. We used CatSalut data from Catalonia to assess the implementation of local recommendations. RESULTS: In England, 66 assessments were undertaken by the National Institute for Health and Care Excellence (NICE), using a standardised methodology. In Spain, there were 79 reports undertaken by a range of bodies using a shared process and coordinated through the GENESIS collaboration; the assessment methods used varied substantially. Overall, the recommendations in the two jurisdictions were similar. Regression analyses indicate that where there is a positive recommendation by HTA bodies, the usage of the medicine responds most strongly (p < 0.001) in Catalonia (4.892), followed by England (3.120) and Spain (1.693). CONCLUSIONS: This study suggests that medicine utilisation does respond to the positive recommendations of HTA bodies. However, if HTA capacity is organised primarily regionally, considerable effort may be required in coordination, to ensure consistent and rigorous assessments and adequate implementation of HTA findings.
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Recursos em Saúde/estatística & dados numéricos , Medicamentos sob Prescrição/economia , Medicina Estatal/organização & administração , Avaliação da Tecnologia Biomédica/organização & administração , Análise Custo-Benefício , Inglaterra , Humanos , EspanhaRESUMO
Multiple Criteria Decision Analysis (MCDA) has emerged as a methodology for Health Technology Assessment (HTA). However, limited empirical evidence is available on its use by decision-makers; where available, it only comes from single-setting exercises, while cross-country comparative studies are unavailable. This study applies the Advance Value Framework (AVF), an MCDA methodology for HTA based on multi-attribute value theory, through a series of case studies with decision-makers in four countries, to explore its feasibility and compare decision-makers' value preferences and results. The AVF was applied in the evaluation of three drugs for metastatic, castrate resistant, prostate cancer (abiraterone, cabazitaxel and enzalutamide) in the post-chemotherapy indication. Decision conferences were organised in four European countries in collaboration with their HTA or health insurance organisations by involving relevant assessors and experts: Sweden (TLV), Andalusia/Spain (AETSA), Poland (AOTMiT) and Belgium (INAMI-RIZIV). Participants' value preferences, including performance scoring and criteria weighting, were elicited through a facilitated decision-analysis modelling approach using the MACBETH technique. Between 6 and 11 criteria were included in each jurisdiction's value model, allocated across four criteria domains; Therapeutic Benefit criteria consistently ranked first in relative importance across all countries. Consistent drug rankings were observed in all settings, with enzalutamide generating the highest overall weighted preference value (WPV) score, followed by abiraterone and cabazitaxel. Dividing drugs' overall WPV scores by their costs produced the lowest "cost per unit of value" for enzalutamide, followed by abiraterone and cabazitaxel. These results come in contrast with the actual country HTA recommendations and pricing decisions. Overall, although some differences in value preferences were observed between countries, drug rankings remained the same. The MCDA methodology employed could act as a decision support tool in HTA, due to the transparency in the construction of value preferences in a collaborative manner.
Assuntos
Técnicas de Apoio para a Decisão , Avaliação da Tecnologia Biomédica , Bélgica , Tomada de Decisões , Europa (Continente) , Humanos , Polônia , Espanha , SuéciaRESUMO
Urolithin A (Uro-A) is an anti-inflammatory and cancer chemopreventive metabolite produced by the gut microbiota from the polyphenol ellagic acid. However, in vivo conjugation of Uro-A to Uro-A glucuronide (Uro-A glur) dramatically hampers its activity. We describe here for the first time the tissue deconjugation of Uro-A glur to Uro-A after lipopolysaccharide (LPS)-induced inflammation, which could explain the systemic in vivo activity of free Uro-A in microenvironments subjected to inflammatory stimuli.
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Cumarínicos/farmacocinética , Glucuronídeos/farmacocinética , Inflamação/tratamento farmacológico , Animais , Cumarínicos/administração & dosagem , Cumarínicos/química , Ácido Elágico/metabolismo , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Glucuronídeos/administração & dosagem , Glucuronídeos/química , Humanos , Inflamação/metabolismo , Inflamação/microbiologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Monacolin K (MK, lovastatin), a naturally occurring statin, only exerts lipid-lowering effects in its active ß-hydroxy acid form (MKA). This activation was thought to be mediated by the gut microbiota (GM). We report here for the first time that the GM does not convert MK into MKA (a spontaneous pH-dependent conversion) but catabolises MKA. The GM might hamper the lipid-lowering effects by degrading the active metabolite MKA.
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Anticolesterolemiantes/metabolismo , Bactérias/metabolismo , Microbioma Gastrointestinal , Hidroxiácidos/metabolismo , Lovastatina/metabolismo , Adulto , Anticolesterolemiantes/química , Biotransformação , Fezes/microbiologia , Feminino , Humanos , Hidroxiácidos/química , Lovastatina/química , Masculino , Pessoa de Meia-IdadeRESUMO
Background: The aim of this study was to develop a spending predictor model to evaluate the direct costs associated with the management of ABSSSIs from the National health-care provider's perspective of Italy, Romania, and Spain. Methodology: A decision-analytic model was developed to evaluate the diagnostic and clinical pathways of hospitalized ABSSSI patients based on scientific guidelines and real-world data. A Standard of Care (SoC) scenario was compared with a dalbavancin scenario in which the patients could be discharged early. The epidemiological and cost parameters were extrapolated from national administrative databases (i.e., hospital information system). A probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWA) were performed. Results: Overall, the model estimated an average annual number of patients with ABSSSIs of approximately 50,000 in Italy, Spain, and Romania. On average, the introduction of dalbavancin reduced the length of stay by 3.3 days per ABSSSI patient. From an economic perspective, dalbavancin did not incur any additional cost from the National Healthcare perspective, and the results were consistent among the countries. The PSA and OWA demonstrated the robustness of these results. Conclusion: This model represents a useful tool for policymakers by providing information regarding the economic and organizational consequences of an early discharge approach in ABSSSI management.
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Antibacterianos/administração & dosagem , Modelos Econômicos , Dermatopatias Bacterianas/tratamento farmacológico , Teicoplanina/análogos & derivados , Doença Aguda , Antibacterianos/economia , Simulação por Computador , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Hospitalização/economia , Humanos , Itália , Tempo de Internação , Romênia , Dermatopatias Bacterianas/economia , Espanha , Teicoplanina/administração & dosagem , Teicoplanina/economiaRESUMO
Understanding individuals' response to dietary bioactives is crucial for personalized nutrition. We report here for the first time in a Caucasian cohort (5-90 years, n = 839) that aging is the main factor that determines the gut microbiota involved in the ellagic acid-ellagitannin metabolism (urolithin metabotypes), with potential consequences for human health.
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Envelhecimento/fisiologia , Cumarínicos/metabolismo , Cumarínicos/urina , Ácido Elágico/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Neoplasias Colorretais/metabolismo , Dieta , Feminino , Alimentos , Humanos , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Neoplasias da Próstata/metabolismo , Adulto JovemRESUMO
Gut microbiota dysbiosis alters the intestinal barrier function, increases plasma lipopolysaccharide (LPS) levels, which promotes endotoxemia, and contributes to the onset and development of colorectal cancer (CRC). We report here for the first time the reduction of plasma LPS-binding protein (LBP) levels, a marker of endotoxemia, after pomegranate consumption in newly diagnosed CRC patients.
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Proteínas de Transporte/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/dietoterapia , Endotoxemia/sangue , Lythraceae/metabolismo , Glicoproteínas de Membrana/sangue , Proteínas de Fase Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Endotoxemia/diagnóstico , Biomarcadores Ambientais , Feminino , Frutas/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: In recent years, several studies have shown that the age of the donor may be related to an increase in the occurrence of biliary complications (BCs), which remain the main cause of morbidity after liver transplantation. This study analyzed the type and management of these BCs, the impact of BCs on graft and patient survival rates, and the influence of some characteristics of donors and recipients on BC appearance in patients transplanted with donors 75 years of age or older. PATIENTS AND METHODS: From 2003 to 2016, 100 liver transplantations with donors 75 years of age or older (15.6%) were performed in our hospital. The data were compared with a control group of 400 patients with younger donors (case-control 1:4 per chronology). RESULTS: The BC rate in the group of patients transplanted with organs from elderly donors was 18%, compared to 21.5% in the control group. Specifically, in the immediate post-transplantation period, 14% of the elderly donor group and 13.8% of the control group presented some BCs, with no statistically significant differences in the incidence, type, and treatment of BCs between the two groups. The occurrence of BCs was not a factor associated with graft and patient survival rates. In the global population, donor death by cerebral vascular accident and male donors have influenced the occurrence of BCs. CONCLUSIONS: The advanced age of the donor has not influenced BC rates after transplantation.
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Transplante de Fígado/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Doadores de Tecidos , Fatores Etários , Idoso , Estudos de Casos e Controles , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Sixteen Iberian barrows of the same age with an average initial live weight of 100.1kg were randomly distributed in two groups of eight pigs each. One group was fed healthy acorns and the other group received acorns infested of Curculio sp. The subcutaneous backfat from pigs fed healthy acorns had higher C18:1n-9, MUFA and C20:5n-3 and lower C18:0 and SFA proportions than that from the pigs fed acorns infested with Curculio. The consumption of acorns infested with Curculio sp. led to a reduction of C18:1n-9, MUFA, C18:2n-6, C18:3n-3, C22:5n-3 and PUFA proportions in neutral lipids from Longissimus dorsi muscle with respect to consumption of healthy acorns, whereas in polar lipids it produced a reduction in C18:1n-9, MUFA and C18:4n-3 proportions and an increase in C18:2n-6, C20:4n-6, n-6 and C20:5n-3 proportions and of n-6/n-3 ratio with respect to the healthy acorns consumption. The pigs fed healthy acorns had higher intramuscular fat percentage in Longissimus dorsi than pigs fed with acorns infested with Curculio (9.95 vs 7.09% SEM=0.60).
RESUMO
OBJECTIVE: The aim of the present study is to investigate the effect of antioxidant polyphenol-rich pomegranate juice (PJ) supplementation for 5 weeks on patients with stable chronic obstructive pulmonary disease (COPD), since the oxidative stress plays a major role in the evolution and pathophysiology of COPD. DESIGN: A randomized, double-blind, placebo-controlled trial was conducted. SUBJECTS: A total of 30 patients with stable COPD were randomly distributed in two groups (15 patients each). INTERVENTIONS: Both groups consumed either 400 ml PJ daily or matched placebo (synthetic orange-flavoured drink) for 5 weeks. Trolox Equivalent Antioxidant Capacity (TEAC) of PJ, blood parameters (14 haematological and 18 serobiochemical), respiratory function variables, bioavailability of PJ polyphenols (plasma and urine) and urinary isoprostane (8-iso-PGF(2alpha)) were evaluated. RESULTS: The daily dose of PJ (containing 2.66 g polyphenols) provided 4 mmol/l TEAC. None of the polyphenols present in PJ were detected in plasma or in urine of volunteers. The most abundant PJ polyphenols, ellagitannins, were metabolized by the colonic microflora of COPD patients to yield two major metabolites in both plasma and urine (dibenzopyranone derivatives) with no TEAC. No differences were found (P > 0.05) between PJ and placebo groups for any of the parameters evaluated (serobiochemical and haematological), urinary 8-iso-PGF(2alpha), respiratory function variables and clinical symptoms of COPD patients. CONCLUSIONS: Our results suggest that PJ supplementation adds no benefit to the current standard therapy in patients with stable COPD. The high TEAC of PJ cannot be extrapolated in vivo probably due to the metabolism of its polyphenols by the colonic microflora. The understanding of the different bioavailability of dietary polyphenols is critical before claiming any antioxidant-related health benefit. SPONSORSHIP: 'Fundación Séneca' (Murcia, Spain), Project PB/18/FS/02 and Spanish CICYT, Project AGL2003-02195.
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Antioxidantes/administração & dosagem , Bebidas , Flavonoides/administração & dosagem , Lythraceae/química , Fenóis/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/terapia , Antioxidantes/metabolismo , Bactérias Anaeróbias/metabolismo , Disponibilidade Biológica , Colo/microbiologia , Método Duplo-Cego , Fermentação , Flavonoides/metabolismo , Humanos , Taninos Hidrolisáveis/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Fenóis/metabolismo , Polifenóis , Testes de Função RespiratóriaRESUMO
The ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP) is an efflux protein involved in the bioavailability and milk secretion of endogenous and exogenous compounds, actively affecting milk composition. A limited number of physiological substrates have been identified. However, no studies have reported the specific effect of this polymorphism on the secretion into milk of compounds implicated in milk quality such as vitamins or endogenous compounds. The bovine ABCG2 Y581S polymorphism is described as a gain-of-function polymorphism that increases milk secretion and decreases plasma levels of its substrates. This work aims to study the impact of Y581S polymorphism on plasma disposition and milk secretion of compounds such as riboflavin (vitamin B2), enterolactone, a microbiota-derived metabolite from the dietary lignan secoisolariciresinol and uric acid. In vitro transport of these compounds was assessed in MDCK-II cells overexpressing the bovine ABCG2 (WT-bABCG2) and its Y581S variant (Y581S-bABCG2). Plasma and milk levels were obtained from Y/Y homozygous and Y/S heterozygous cows. The results show that riboflavin was more efficiently transported in vitro by the Y581S variant, although no differences were noted in vivo. Both uric acid and enterolactone were substrates in vitro of the bovine ABCG2 variants and were actively secreted into milk with a two-fold increase in the milk/plasma ratio for Y/S with respect to Y/Y cows. The in vitro ABCG2-mediated transport of the drug mitoxantrone, as a model substrate, was inhibited by enterolactone in both variants, suggesting the possible in vivo use of this enterolignan to reduce ABCG2-mediated milk drug transfer in cows. The Y581S variant was inhibited to a lesser extent probably due to its higher transport capacity. All these findings point to a significant role of the ABCG2 Y581S polymorphism in the milk disposition of enterolactone and the endogenous molecules riboflavin and uric acid, which could affect both milk quality and functionality.
Assuntos
4-Butirolactona/análogos & derivados , Transportadores de Cassetes de Ligação de ATP/genética , Bovinos/fisiologia , Leite/metabolismo , Riboflavina/metabolismo , Ácido Úrico/metabolismo , 4-Butirolactona/análise , 4-Butirolactona/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico , Butileno Glicóis/química , Butileno Glicóis/metabolismo , Bovinos/genética , Bovinos/metabolismo , Cães , Feminino , Lactação , Lignanas/análise , Lignanas/química , Lignanas/metabolismo , Células Madin Darby de Rim Canino , Leite/química , Mitoxantrona/metabolismo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The study presented here demonstrates that the antihypertensive drug captopril ([2S]-N-[3-mercapto-2-methylpropionyl]-L-proline) is an irreversible non-competitive inhibitor and an irreversible competitive inhibitor of the monophenolase and diphenolase activities of mushroom tyrosinase when L-tyrosine and L-DOPA were assayed spectrophotometrically in vitro, respectively. Captopril was rendered unstable by tyrosinase catalysis because of the interaction between the enzymatic-generated product (o-quinone) and captopril to give rise to a colourless conjugate. Therefore, captopril was able to prevent melanin formation. The spectrophotometric recordings of the inhibition of tyrosinase by captopril were characterised by the presence of a lag period prior to the attainment of an inhibited steady state rate. The lag period corresponded to the time in which captopril was reacting with the enzymatically generated o-quinone. Increasing captopril concentrations provoked longer lag periods as well as a concomitant decrease in the tyrosinase activity. Both lag period and steady state rate were dependent of captopril, substrate and tyrosinase concentrations. The inhibition of both monophenolase and diphenolase activities of tyrosinase by captopril showed positive kinetic co-operativity which arose from the protection of both substrate and o-quinone against inhibition by captopril. Inhibition experiments carried out using a latent mushroom tyrosinase demonstrated that captopril only bound the enzyme at its active site. The presence of copper ions only partially prevented but not reverted mushroom tyrosinase inhibition. This could be due to the formation of both copper-captopril complex and disulphide interchange reactions between captopril and cysteine rich domains at the active site of the enzyme.