Ultra-processed Foods and Cardiovascular Diseases: Potential Mechanisms of Action

Ultra-processed foods are industrially manufactured ready-to-eat or ready-to-heat formulations containing food additives and little or no whole foods, in contrast to processed foods, which are whole foods preserved by traditional techniques such as canning or pickling. Recent epidemiological studies suggest that higher consumption of ultra-processed food is associated with increased risk of cardiovascular disease (CVD). However, epidemiological evidence needs to be corroborated with criteria of biological plausibility. This review summarizes the current evidence on the putative biological mechanisms underlying the associations between ultra-processed foods and CVD. Research ranging from laboratory-based to prospective epidemiological studies and experimental evidence suggest that ultra-processed foods may affect cardiometabolic health through a myriad of mechanisms, beyond the traditionally recognized individual nutrients. Processing induces significant changes to the food matrix, for which ultra-processed foods may affect health outcomes differently than unrefined whole foods with similar nutritional composition. Notably, the highly degraded physical structure of ultra-processed foods may affect cardiometabolic health by influencing absorption kinetics, satiety, glycemic response, and the gut microbiota composition and function. Food additives and neo-formed contaminants produced during processing may also play a role in CVD risk. Key biological pathways include altered serum lipid concentrations, modified gut microbiota and host–microbiota interactions, obesity, inflammation, oxidative stress, dysglycemia, insulin resistance, and hypertension. Further research is warranted to clarify the proportional harm associated with the nutritional composition, food additives, physical structure, and other attributes of ultra-processed foods. Understanding how ultra-processing changes whole foods and through which pathways these foods affect health is a prerequisite for eliminating harmful processing techniques and ingredients.     

Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice

OBJECTIVES: Models for the development of new treatment options in vestibular schwannoma (VS) treatment are lacking. The purpose of this study is to establish a quantifiable human VS xenograft model in mice. STUDY DESIGN AND METHODS: Both rat malignant schwannoma cells (KE-F11 and RT4) and human malignant schwannoma (HMS-97) cells were implanted near the sciatic nerve in the thigh of severe combined immunodeficiency (SCID) mice. Additionally, human benign VS specimens were implanted in another set of SCID mice. Three-dimensional tumor volumes were calculated from magnetic resonance images over the next 6 months. RESULTS: Mice implanted with malignant schwannoma cells developed visible tumors within 2 weeks. Imaging using a 4.7-tesla magnetic resonance imaging and immunohistopathologic examination identified solid tumors in all KE-F11 and HMS-97 xenografts, whereas RT4 xenografts consistently developed cystic schwannomas. VS xenografts demonstrated variability in their growth rates similar to human VS. The majority of VS xenografts did not grow but persisted throughout the study, whereas two of 15 xenografts grew significantly. Histopathologic examination and immunohistochemistry confirmed that VS xenografts retained their original microscopic and immunohistochemical characteristics after prolonged implantation. CONCLUSIONS: This study describes the first animal model for cystic schwannomas. Also, we demonstrate the use of high-field magnetic resonance imaging to quantify VS xenograft growth over time. The VS xenografts represent a model complimentary to Nf2 transgenic and knockout mice for translational VS research.     

Evaluation of Serum Selenium Status by Age and Gender: A Retrospective Observational Cohort Study in Western Romania

Selenium, residing in a series of selenoproteins, plays an important role in both female and male reproductive function. Of particular significance for reproduction is the antioxidant glutathione peroxidase (GPx), a main selenoenzyme, whose level is regulated by the availability of Se in the body. We hypothesized that changes in Se status, closely related to GPx activity, would result in an increased risk of reproductive dysfunction in individuals. We retrospectively investigated the serum selenium (SeS) concentrations of 1264 apparently healthy people, aged 16–89 years, from Western Romania. The general analysis revealed a non-normal SeS distribution with a median SeS of 100.26 ± 18.32 μg/L and a significant difference in SeS levels between age groups. The analysis of the young group (16–35 years) revealed that up to 50% of individuals did not reach the SeS threshold corresponding to maximum GPx activity (80 μg/L), and a significant imbalance between the genders was apparent when looking at SeS values outside the range. Our results correlated with the general diminished reproductive ability registered in Romania during the last few years. Serum selenium content proves to offer a proper reflection of the fertility competence of the young population, and its monitoring is important for guiding dietary adjustments and attaining normal reproductive function.     

Poly(urethane-parabanic acid)s

Oligoureas with diisocyanato end groups (6a – f) were transformed into the respective parabanic acid derivatives (7a – f) with the aid of oxalyl chloride (2) . In the reaction of 2 with certain diurea model compounds (12) in 1,2-dichloroethane at room temperature besides the corresponding parabanic acids, diurea dihydrochlorides were formed. Their solutions in 1,2-dichloroethane exhibit electrical conductivity. IR spectra confirm their structure. The reaction of the α,ω-diisocyanatopoly(parabanic acid)s with diols (8a – e) led to copolymers and block copolymers, poly(urethane-parabenic acid)s. The experimental conditions and the influence of the structure of the polymers on certain properties of the final products were investigated.     

Characterization and pharmacokinetic study of recombinant human N-acetylgalactosamine-6-sulfate sulfatase

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The aims of this study were to establish Chinese hamster ovary (CHO) cells overexpressing recombinant human GALNS (rhGALNS) and to assess pharmacokinetics and tissue distribution of purified enzymes by using MPS IVA knock-out mouse (Galns(-/-)). The CHO-cell derived rhGALNS was purified from the media by a two-step affinity chromatography procedure. The rhGALNS was administered intravenously to 3-month-old Galns(-/-) mice at a single dose of 250U/g of body weight. The treated mice were examined by assaying the GALNS activity at baseline and up to 240min to assess clearance of the enzyme from blood circulation. The mice were sacrificed 4h after infusion of the enzyme to study the enzyme distribution in tissues. The rhGALNS was purified 1317-fold with 71% yield. The enzyme was taken up by Galns(-/-) chondrocytes (150U/mg/15h). The uptake was inhibited by mannose-6-phosphate. The enzyme activity disappeared from circulation with a half-life of 2.9min. After enzyme infusion, the enzyme was taken up and detected in multiple tissues (40.7% of total infused enzymes in liver). Twenty-four hours after a single infusion of the fluorescence-labeled enzymes into MPS IVA mice, biodistribution pattern showed the amount of tagged enzyme retained in bone, bone marrow, liver, spleen, kidney, and heart. In conclusion, we have shown that the phosphorylated rhGALNS is delivered to multiple tissues, including bone, and that it functions bioactively in Galns(-/-) chondrocytes implying a potential enzyme replacement treatment.     

Perspectives on optimizing trial design and endpoints in peripheral arterial disease: a case for imaging-based surrogates as endpoints of functional efficacy

Surrogate endpoints are important for validation of mechanism, early proof of concept, and the rational design of clinical trials for regulatory approval of drugs. The recent failure of several drugs in peripheral arterial disease (PAD) and in atherosclerosis highlights the importance of understanding drug effect and is a clarion call for better endpoints. This review focuses on aspects relating to the current state of surrogate endpoints in PAD and reviews emerging endpoints using imaging approaches that may have the potential of improving study design in PAD.     

Comparison of a single shot T1-weighted in- and out-of-phase magnetization prepared gradient recalled echo with a standard two-dimensional gradient recalled echo: preliminary findings

Purpose:

To compare in‐phase (IP) /out‐of‐phase (OP) single shot magnetization‐prepared gradient‐recalled‐echo (MP‐GRE) with a standard two‐dimensional gradient‐recalled‐echo (2D‐GRE), and to compare image quality of MP‐GRE in cooperative and noncooperative subjects.

Materials and Methods:

Ninety‐six consecutive subjects (52 males, 44 females; mean age, 53.2 ± 16.7 years), both cooperative (n = 73) and noncooperative (n = 23) subjects who had MRI examinations including precontrast T1‐weighted IP/OP MP‐GRE with or without IP/OP 2D‐GRE were included in the study. The sequences were independently qualitatively evaluated by two radiologists. Quantitative analysis of liver fat index, signal‐to‐noise ratio (SNR) and liver‐lesion contrast‐to‐noise ratio (CNR) was also performed. Data were subjected to statistical analysis.

Results:

The visual detection of the presence or absence of liver steatosis showed no differences between 2D‐GRE and MP‐GRE imaging (k = 1). Minor differences were observed on image quality between MP‐GRE and 2D‐GRE in cooperative subjects, and between MP‐GRE sequences performed in cooperative and noncooperative subjects. Liver fat index results were strongly positively correlated (r = .98; 95% confidence interval [CI] 0.97 to 0.98; P < .0001). Intercept (.14; 95% CI .13 to .15; P < .0001) and slope (.83; 95% CI .79 to .86; P < .0001) were statistically significant.

Conclusion:

IP/OP MP‐GRE and 2D‐GRE comparably demonstrate the presence or absence of hepatic steatosis. Image quality of MP‐GRE was also comparable to 2D‐GRE, and was not substantially adversely affected if subjects were unable to cooperate with breathholding instructions. J. Magn. Reson. Imaging 2011;33:1482–1490. © 2011 Wiley‐Liss, Inc.