Effect of Raw and Roasted Phoenix dactylifera L. Seed Polyphenols Extracts on Suppression of Angiogenesis in Endothelial Cells.

Date seed is a by-product of Phoenix dactylifera L. fruit which is well recognized for its polyphenols content and numerous health-beneficial effects. Due to the increasing interest in natural phytochemicals with antioxidant activities, the present study aimed to extract polyphenols from both raw and roasted date seeds and investigate the anti-angiogenic effect of these two extracts (raw and roasted date seed polyphenols extracts (DSPE) at 25 and 50 µg/mL) using human microvascular endothelial cells (HMVEC). Our results showed that both raw and roasted DSPE suppressed some angiogenesis features in a dose-dependent manner including cell proliferation, migration, and capillary-like structure formation, of which raw DSPE was more potent inhibitor than roasted DSPE. Reduction in reactive oxygen species, as well as enhancement of superoxide dismutase activity occurred using both raw and roasted date seed polyphenols extracts. However, no changes were observed in advanced oxidation protein products versus control. Taken together, our data indicated that raw and roasted DSPE possess antioxidant activity, which suggested their potential use as a source of polyphenols with anti-angiogenic properties. Nevertheless, further studies are required to explore the underlying mechanisms responsible for their anti-angiogenic activities.

Unveiling the Metabolic Effects of Glycomacropeptide.

For many years, the main nitrogen source for patients with phenylketonuria (PKU) was phenylalanine-free amino acid supplements. Recently, casein glycomacropeptide (GMP) supplements have been prescribed due to its functional and sensorial properties. Nevertheless, many doubts still persist about the metabolic effects of GMP compared to free amino acids (fAA) and intact proteins such as casein (CAS). We endeavour to compare, in rats, the metabolic effects of different nitrogen sources. Twenty-four male Wistar rats were fed equal energy density diets plus CAS (control, n = 8), fAA (n = 8) or GMP (n = 8) for 8 weeks. Food, liquid intake and body weight were measured weekly. Blood biochemical parameters and markers of glycidic metabolism were assessed. Glucagon-like peptide-1 (GLP-1) was analysed by ELISA and immunohistochemistry. Food intake was higher in rats fed CAS compared to fAA or GMP throughout the treatment period. Fluid intake was similar between rats fed fAA and GMP. Body weight was systematically lower in rats fed fAA and GMP compared to those fed CAS, and still, from week 4 onwards, there were differences between fAA and GMP. None of the treatments appeared to induce consistent changes in glycaemia, while insulin levels were significantly higher in GMP. Likewise, the production of GLP-1 was higher in rats fed GMP when compared to fAA. Decreased urea, total protein and triglycerides were seen both in fAA and GMP related to CAS. GMP also reduced albumin and triglycerides in comparison to CAS and fAA, respectively. The chronic consumption of the diets triggers different metabolic responses which may provide clues to further study potential underlying mechanisms.

What is the relevance of percutaneous endoscopic gastrostomy on the survival of patients with amyotrophic lateral sclerosis?

Percutaneous endoscopic gastrostomy (PEG) is a standard procedure for feeding dysphagic amyotrophic lateral sclerosis (ALS) patients. Nevertheless, the effect of prognostic factors influencing survival after PEG remains unclear. We aimed to evaluate the prognostic value of several clinical features on survival after PEG placement. This study investigated 151 patients with ALS, in whom a PEG was inserted over the last 16 years in our centre. Survival curves were determined by Kaplan-Meier and the analysis of potential prognostic factors was performed by a Cox regression model. The overall median survival was 32 months, longer in spinal-onset disease patients - 42 vs. 29 months in bulbar-onset patients (p < 0.001). Median survival after PEG placement was 7.5 months, similar in both bulbar- and spinal-onset patients, 7.9 vs. 7.1 months, respectively. Thirteen percent of patients died within one month after PEG placement; this short-term survival was influenced by low forced vital capacity (FVC < 50%). In a multivariate analysis, only older age at disease onset was independently associated with poor outcome after PEG placement. In conclusion, survival after PEG placement was similar in bulbar- and spinal-onset patients, suggesting that the latter were in a more advanced stage at the time of PEG placement. Low FVC was associated with higher risk of short-term mortality. Older age at disease onset was associated with poorer outcome in bulbar-onset patients. Younger bulbar-onset patients are those who benefited most from PEG.

Continuous use of glycomacropeptide in the nutritional management of patients with phenylketonuria: a clinical perspective.

BACKGROUND: In phenylketonuria (PKU), modified casein glycomacropeptide supplements (CGMP-AA) are used as an alternative to the traditional phenylalanine (Phe)-free L-amino acid supplements (L-AA). However, studies focusing on the long-term nutritional status of CGMP-AA are lacking. This retrospective study evaluated the long-term impact of CGMP-AA over a mean of 29 months in 11 patients with a mean age at CGMP-AA onset of 28 years (range 15-43) [8 females; 2 hyperphenylalaninaemia (HPA), 3 mild PKU, 3 classical PKU and 3 late-diagnosed]. Outcome measures included metabolic control, anthropometry, body composition and biochemical parameters. RESULTS: CGMP-AA, providing 66% of protein equivalent intake from protein substitute, was associated with no significant change in blood Phe with CGMP-AA compared with baseline (562 ± 289 µmol/L vs 628 ± 317 µmol/L; p = 0.065). In contrast, blood tyrosine significantly increased on CGMP-AA (52.0 ± 19.2 µmol/L vs 61.4 ± 23.8 µmol/L; p = 0.027). CONCLUSIONS: Biochemical nutritional markers remained unchanged which is an encouraging finding in adults with PKU, many of whom are unable to maintain full adherence with nutritionally fortified protein substitutes. Longitudinal, prospective studies with larger sample sizes are necessary to fully understand the metabolic impact of using CGMP-AA in PKU.

Does adipose tissue inflammation drive the development of non-alcoholic fatty liver disease in obesity?

Obesity, an increasingly common problem in modern societies, is associated with acquired metabolic disturbances. In this perspective, the development of insulin resistance is now recognized to be initiated by inflammation of the adipose tissue, but the events that lead to this inflammation are still vague. Furthermore, visceral adipose tissue plays a significant role in obesity pathophysiology and in its clinical effects, such as non-alcoholic fatty liver disease (NAFLD). Among the possible mechanisms linking NAFLD and obesity, we focused on Visfatin/NAMPT, mostly produced by macrophages infiltrated in adipose tissue and a biomarker of the inflammatory cascade affecting hepatic inflammation in NAFLD. We also addressed the signalling pathway triggered by the binding of VEGF-B to its receptor, which mediates lipid fluxes throughout the body, being a promising target to prevent ectopic lipid accumulation. We reviewed the available literature on the topic and we suggest a crosstalk between adipose tissue inflammation and NAFLD in order to provide new insights about the putative mechanisms involved in the development of NAFLD in the obesity context. A better understanding of the pathophysiological processes underlying NAFLD will allow the development of new therapeutic approaches.

The Use of Glycomacropeptide in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis.

In phenylketonuria (PKU), synthetic protein derived from L-amino acids (AAs) is essential in a low-phenylalanine (Phe) diet. Glycomacropeptide (GMP), an intact protein, is very low in Phe in its native form. It has been modified and adapted for PKU to provide an alternative protein source through supplementation with rate-limiting amino acids (GMP-AAs), although it still contains residual Phe. This review aims to systematically evaluate published intervention studies on the use of GMP-AAs in PKU by considering its impact on blood Phe control (primary aim) and changes in tyrosine control, nutritional biomarkers, and patient acceptability or palatability (secondary aims). Four electronic databases were searched for articles published from 2007 to June 2018. Of the 274 studies identified, only eight were included. Bias risk was assessed and a quality appraisal of the body of evidence was completed. A meta-analysis was performed with two studies with adequate comparable methodology which showed no differences between GMP-AAs and AAs for any of the interventions analysed. This work underlines the scarcity and nature of studies with GMP-AAs interventions. All were short-term with small sample sizes. There is a need for better-designed studies to provide the best evidence-based recommendations.

Special low protein foods for phenylketonuria: availability in Europe and an examination of their nutritional profile.

BACKGROUND: Special low protein foods (SLPF) are essential in the nutritional management of patients with phenylketonuria (PKU). The study objectives were to: 1) identify the number of SLPF available for use in eight European countries and Turkey and 2) analyse the nutritional composition of SLPF available in one of these countries. METHODS: European Nutritionist Expert Panel on PKU (ENEP) members (Portugal, Spain, Belgium, Italy, Germany, Netherlands, UK, Denmark and Turkey) provided data on SPLF available in each country. The nutritional composition of Portuguese SLPF was compared with regular food products. RESULTS: The number of different SLPF available in each country varied widely with a median of 107 [ranging from 73 (Portugal) and 256 (Italy)]. Food analysis of SLPF available from a single country (Portugal) indicated that the mean phenylalanine content was higher in low protein baby cereals (mean 48 mg/100 g) and chocolate/energy bars/jelly (mean 41 mg/100 g). The energy content of different foods from a sub-group of SLPF (cookies) varied widely between 23 and 96 kcal/cookie. Low protein bread had a high fat content [mean 5.8 g/100 g (range 3.7 to 10)] compared with 1.6 g/100 g in regular bread. Seven of the 12 SLPF sub-groups (58 %) did not declare any vitamin content, and only 4 (33 %) identified a limited number of minerals. CONCLUSIONS: Whilst equal and free access to all SLPF is desirable, the widely variable nutritional composition requires careful nutritional knowledge of all products when prescribed for individual patients with PKU. There is a need for more specific nutritional standards for special low protein foods.