The Use of Proton Pump Inhibitors May Increase Symptoms of Muscle Function Loss in Patients with Chronic Illnesses

Long-term use of proton pump inhibitors (PPIs) is common in patients with muscle wasting-related chronic diseases. We explored the hypothesis that the use of PPIs may contribute to a reduction in muscle mass and function in these patients. Literature indicates that a PPI-induced reduction in acidity of the gastrointestinal tract can decrease the absorption of, amongst others, magnesium. Low levels of magnesium are associated with impaired muscle function. This unwanted side-effect of PPIs on muscle function has been described in different disease backgrounds. Furthermore, magnesium is necessary for activation of vitamin D. Low vitamin D and magnesium levels together can lead to increased inflammation involved in muscle wasting. In addition, PPI use has been described to alter the microbiota’s composition in the gut, which might lead to increased inflammation. However, PPIs are often provided together with nonsteroidal anti-inflammatory drugs (NSAIDs), which are anti-inflammatory. In the presence of obesity, additional mechanisms could further contribute to muscle alterations. In conclusion, use of PPIs has been reported to contribute to muscle function loss. Whether this will add to the risk factor for development of muscle function loss in patients with chronic disease needs further investigation

Peanut allergen Ara h 6 is detectable in blood transfusion products

Peanut allergen Ara h 6 is known to maintain IgE‐binding capacity upon exposure to digestive enzymes1 and its presence in circulation after consumption of peanut has been demonstrated.2,3 Therefore, it has been speculated that food‐derived allergens could be transferred via blood transfusion products, causing an allergic reaction in food-allergic recipients.4,5 However, in published case reports, presence of food allergen in donated material could not be confirmed due to lack of remaining transfusion material and/or lack of sensitive analytical methods. Using a newly developed sensitive immune‐assay for detecting Ara h 6 in human serum, we now report to what extent consumed peanut allergens can be present in blood transfusion materials and estimate the associated risk for peanut‐allergic recipients

A diet rich in fish oil and Leucine Ameliorates Hypercalcemia in tumour-induced cachectic mice

Background: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). Methods: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. Results: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. Conclusion: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour

A Logical Study of Distributed Transition Systems

AbstractWe extend labelled transition systems to distributed transition systems by labelling the transition relation with a finite set of actions, representing the fact that the actions occur as a concurrent step. We design an addition-based temporal logic in which one can explicity talk about steps. The logic is studied to establish a variety of positive and negative results in terms of axiomatizability and decidability. Our positive results show that the step notion is amenable to logical treatment via standard techniques. They also help us to obtain a logical characterization of two well known models for distributed systems: labelled elementary net systems and labelled prime event structures. Our negative results show that demanding deterministic structures when dealing with a "non-interleaved" notion of transitions is, from a logical standpoint, very expressive. They also show that another well known model of distributed systems called asynchronous transition systems exhibits a surprising amount of expressive power in a natural logical setting

Markers for Immunological Resilience: Effects of Moderate- and High-Intensity Endurance Exercise on the Kinetic Response of Leukocyte Subsets

The kinetic responses of leukocyte subsets to exercise and their recovery may serve as indicators of immunological resilience. These time-dependent responses were investigated in healthy young men using a bicycle ergometer test. Fifteen recreationally active male cyclists (20–35 years, VO2max 56.9 ± 3.9 mL kg−1 min−1) performed four exercise protocols with a 1 h duration in a cross-over design: at 70% of the maximal workload (Wmax) in a hydrated and a mildly dehydrated state, at 50% of the Wmax, and intermittently at 85/55% of the Wmax in blocks of 2 min. The numbers of lymphocytes, monocytes, neutrophils, eosinophils, basophils, thrombocytes, and NK cells (CD16 and CD56) were measured at different time points up to 24 h post-exercise. The total leukocyte counts and those of most subsets increased from the start of the exercise, peaking after 30–60 min of exercising. The neutrophil numbers, however, peaked 3 h post-exercise. The CD16brightCD56dim NK cells showed a 1.5-fold increase compared to the CD16brightCD56bright NK cells. Other than for MCP-1, no significant differences were found in the serum cytokine levels. Our results show that exercise intensity is reflected in different time-dependent changes in leukocyte subsets, which supports the concept that the exchange of immune cells between peripheral blood and tissues contributes to enhanced immune surveillance during strenuous exercise

Salivary concentrations of secretory leukocyte protease inhibitor and matrix metallopeptidase-9 following a single bout of exercise are associated with intensity and hydration status

AIM: To investigate the effects of exercise on salivary concentrations of inflammatory markers by analyzing a panel of 25 inflammatory markers in subjects who had participated in bicycle ergometer tests varying in workload and hydration status. METHODS: Fifteen healthy young men (20-35 years) had performed 4 different exercise protocols of 1 hour duration in a randomly assigned cross-over design, preceded by a rest protocol. Individual workloads depended on participant's pre-assessed individual maximum workload (Wmax): rest (protocol 1), 70% Wmax in hydrated (protocol 2) and dehydrated (protocol 3) state, 50% Wmax (protocol 4) and intermittent 85%/55% Wmax in 2 min blocks (protocol 5). Saliva samples were collected before (T0) and immediately after exercise (T1), and at several time points after exercise (2 hours (T3), 3 hours (T4), 6 hours (T5) and 24 hours (T6)). Secretory Leukocyte Protease Inhibitor (SLPI), Matrix Metallopeptidase-9 (MMP-9) and lactoferrin was analyzed using a commercial ELISA kit, a panel of 22 cytokines and chemokines were analyzed using a commercial multiplex immunoassay. Data was analyzed using a multilevel mixed linear model, with multiple test correction. RESULTS: Among a panel of 25 inflammatory markers, SLPI concentrations were significantly elevated immediately after exercise in all protocols compared to rest and higher concentrations reflected the intensity of exercise and hydration status. MMP-9 showed a significant increase in the 70% Wmax dehydrated, 50% Wmax and intermittent protocols. CONCLUSIONS: Salivary concentrations of SLPI and MMP-9 seem associated with exercise intensity and hydration status and may offer non-invasive biomarkers to study (local) inflammatory responses to different exercise intensities in human studies

Appetite Control across the Lifecourse: The Acute Impact of Breakfast Drink Quantity and Protein Content. The Full4Health Project

Understanding the mechanisms of hunger, satiety and how nutrients affect appetite control is important for successful weight management across the lifecourse. The primary aim of this study was to describe acute appetite control across the lifecourse, comparing age groups (children, adolescents, adults, elderly), weight categories, genders and European sites (Scotland and Greece). Participants (n = 391) consumed four test drinks, varying in composition (15% (normal protein, NP) and 30% (high protein, HP) of energy from protein) and quantity (based on 100% basal metabolic rate (BMR) and 140% BMR), on four separate days in a double-blind randomized controlled study. Ad libitum energy intake (EI), subjective appetite and biomarkers of appetite and metabolism (adults and elderly only) were measured. The adults’ appetite was significantly greater than that of the elderly across all drink types (p 0.004) and in response to drink quantities (p 0.001). There were no significant differences in EI between age groups, weight categories, genders or sites. Concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were significantly greater in the elderly than the adults (p 0.001). Ghrelin and fasting leptin concentrations differed significantly between weight categories, genders and sites (p 0.05), while GLP-1 and PYY concentrations differed significantly between genders only (p 0.05). Compared to NP drinks, HP drinks significantly increased postprandial GLP-1 and PYY (p 0.001). Advanced age was concomitant with reduced appetite and elevated anorectic hormone release, which may contribute to the development of malnutrition. In addition, appetite hormone concentrations differed between weight categories, genders and geographical locations

Co-culture of primary rat hepatocytes with rat liver epithelial cells enhances interleukin-6-induced acute-phase protein response

Three different primary rat hepatocyte culture methods were compared for their ability to allow the secretion of fibrinogen and albumin under basal and IL-6-stimulated conditions. These culture methods comprised the co-culture of hepatocytes with rat liver epithelial cells (CC-RLEC), a collagen type I sandwich culture (SW) and a conventional primary hepatocyte monolayer culture (ML). Basal albumin secretion was most stable over time in SW. Fibrinogen secretion was induced by IL-6 in all cell culture models. Compared with ML, CC-RLEC showed an almost three-fold higher fibrinogen secretion under both control and IL-6-stimulated conditions. Induction of fibrinogen release by IL-6 was lowest in SW. Albumin secretion was decreased after IL-6 stimulation in both ML and CC-RLEC. Thus, cells growing under the various primary hepatocyte cell culture techniques react differently to IL-6 stimulation with regard to acute-phase protein secretion. CC-RLEC is the preferred method for studying cytokine-mediated induction of acute-phase proteins, because of the pronounced stimulation of fibrinogen secretion upon IL-6 exposure under these conditions

Let thy food be thy medicine….when possible

There is no evidence that Hippocrates, although being credited for it, ever literally stated ‘let thy food be thy medicine and thy medicine be thy food’. However, yet in line with Hippocrates’ philosophy, we are currently witnessing a reappraisal of the complementarity of nutrition and pharmacology. Recent studies not only underline the therapeutic potential of lifestyle interventions, but are also generating valuable insights in the complex and dynamic transition from health to disease. Next to this, nutritional biology can significantly contribute to the discovery of new molecular targets. It is clear that most of the current top-selling drugs used in chronic cardio-metabolic diseases modulate relatively late-stage complications, which generally indicate already longer existing homeostatic imbalances. Pharmacologists are increasingly aware that typical multifactorial disorders require subtle, multiple target pharmacological approaches, instead of the still often dominating ‘one disease - one target - one drug’ paradigm. This review discusses the recent developments in the pharma-nutrition interface and shows some relevant mechanisms, including receptors and other targets, and examples from clinical practice. The latter includes inflammatory diseases and progressive loss of muscle function. The examples also illustrate the potential of targeted combinations of medicines with nutrition and (or) other life-style interventions, to increase treatment efficacy and (or) reduce adverse effects. More attention to a potentially negative outcome of drug-food combinations is also required, as shown by the example of food-drug interactions. Together, the developments at the food-pharma interface underline the demand for intensified collaboration between the disciplines, in the clinic and in science.</p