Breast milk is known to contain bioactive peptides that are released during digestion, being a major source of bioactive peptides to the new-born, some of which act against invading pathogens. However, the formation of bioactive peptides during digestion of human colostrum remains largely uninvestigated. This study aimed to investigate the formation of peptides during simulated digestion of human colostrum from adult women and to prospect antimicrobial peptides. For this purpose, we used high-resolution MS to monitor the release of peptides during in vitro digestion. Bioinformatics was used for the prospection of antimicrobial activity of peptides. During simulated digestion (oral, gastric and duodenal phases), 2318 peptide sequences derived from 112 precursor proteins were identified. At the end of simulated digestion, casein-derived peptide sequences were the most frequently observed. Among precursors, some proteins were seen for the first time in this study. The resulting peptides were rich in proline, glutamine, valine and leucine residues, providing characteristic traits of antimicrobial peptides. From bioinformatics analysis, seven peptides showed potentially high antimicrobial activity towards bacteria, viruses and fungi, from which the latter was the most prominent predicted activity. Antimicrobial peptides released during digestion may provide a defence platform with controlled release for the new-born.

Alcohol abuse causes severe metabolic abnormalities inducing hepatic damage and malnutrition. Since higher Fischer ratio proteins have therapeutic value in liver diseases, an investigation was undertaken to study the ameliorative effect of the enhanced Fischer ratio flaxseed protein hydrolysate (EFR-FPH) alone and in combination with antioxidant micronutrients on ethanol-induced hepatotoxicity in a rat model. The EFR-FPH was prepared by dual enzymatic hydrolysis and charcoal treatment of flaxseed protein. The ratio of the branched-chain:aromatic amino acids (Fischer ratio) was found to be 7·08. The EFR-FPH, characterised using LC-MS/MS, showed the abundance of free leucine and isoleucine compared with phenylalanine and tyrosine. The matrix-assisted laser desorption/ionisation-time of flight MS analysis revealed the larger peptides present in EFR-FPH with mass 2·3 kDa. The EFR-FPH improved the nutritional status, liver function and antioxidant defense in the ethanol hepatotoxicity-induced rat model. The hepatoprotective effect of EFR-FPH was significantly enhanced when combined with selenium or vitamin E. Ethanol-induced changes in the liver tissue were effectively suppressed in the groups receiving EFR-FPH. Flaxseed-based hepatoprotective dietary supplement was formulated incorporating an optimum level of EFR-FPH (10 %) based on sensory acceptability and was fortified with selenium and vitamin E. The hepatoprotective formulation significantly lowered aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin by 47, 61, 55 and 78 %, respectively, and improved the antioxidant defense in the ethanol hepatotoxicity-induced rat model. The current investigation suggests that EFR-FPH in synergy with antioxidant micronutrients is potent in ameliorating ethanol-induced hepatotoxicity and has a potential to form a hepatoprotective dietary supplement.

People with Multiple Sclerosis (MS) undertake insufficient physical activity based on current guidelines. Recent work points to the benefits of increasing the amount of time spent in all non-sedentary physical activity. The current study sought to explore the potential benefits to community participation, as well as examine factors predictive, of engagement in ‘habitual’ and/or low-intensity physical activity. Seventy-four people with MS were compared to 67 healthy controls using the Frenchay Activities Index (FAI). Findings revealed differences in habitual activity level (p < .001), and low-intensity physical activity (p < .001), with people with MS having a lower level of engagement than healthy people. After controlling for the impact of MS on mobility, years since symptom onset, physical fatigue and reduced positive affect were the most significant predictors of engagement in ‘at least weekly’ low-intensity physical activity. Higher frequency of low-intensity physical activity was significantly associated with greater home, social and occupational participation (all p < .05), and physical health status (p < .01), but not mental health status (p = .964) in people with MS. Results suggest that improving habitual activity level and engagement in low-intensity physical activity may be of benefit for people with MS.

The majority of children with Down syndrome (DS) develop Alzheimer's disease (AD) at an early age. Although long-chain n-3 fatty acids (FA) are protective of neurodegeneration, little is known about the FA status in DS. In the present study, we aimed to investigate whether children with DS presented altered plasma and erythrocyte membrane phospholipids (PL) FA composition, when compared with their non-affected siblings. Venous blood samples were analysed for plasma and erythrocyte membrane FA composition by TLC followed by GC techniques. Lipid molecular species were determined by electrospray ionisation/tandem MS (ESI-MS/MS). FA analysis measured by standard GC showed an increased concentration of MUFA and a decreased concentration of plasmalogens in major PL fractions, but there were no differences in the concentrations of arachidonic acid or DHA. However, as identified by ESI-MS/MS, children with DS had increased levels of the following erythrocyte PL molecular species: 16 : 0–16 : 0, 16 : 0–18 : 1 and 16 : 0–18 : 2n-6, with reduced levels of 16 : 0–20 : 4n-6 species. Children with DS presented significantly higher levels of MUFA in both plasma and erythrocyte membrane, as well as higher levels of saturated and monounsaturated molecular species. Of interest was the almost double proportion of 16 : 0–18 : 2n-6 and nearly half the proportion of 16 : 0–20 : 4n-6 of choline phosphoacylglycerol species in children with DS compared with their non-affected siblings. These significant differences were only revealed by ESI-MS/MS and were not observed in the GC analysis. Further investigations are needed to explore molecular mechanisms and to test the association between the pathophysiology of DS and the risk of AD.

Systemic lupus erythematosus (SLE) and multiple sclerosis (MS) are chronic immunologic diseases that can cause cognitive dysfunction. MS is a central nervous system (CNS) disease characterized by demyelination and progressive brain atrophy. SLE is an autoimmune disease capable of damaging multiple organ systems, including the CNS. Cognitive disturbances are seen in both SLE and MS. The present study is concerned with understanding the similarities and differences between the cognitive profiles of SLE and MS as well as the relationship between cognitive impairment and vocational disability in these patients. We examined 47 SLE patients, 47 MS patients, and 44 healthy controls. The groups were well matched on demographics and the patient groups were also matched on disease duration and severity. Group comparisons revealed that generative verbal fluency and visual-spatial memory are more profoundly affected in MS than SLE; whereas depression, fatigue, and working memory deficits are similarly involved in both diseases. Logistic regression analysis revealed that executive function, in particular, was predictive of vocational outcomes in SLE and MS patients. (JINS, 2012, 18, 530–540)

The non-extractable fraction of many fruit and vegetables contains putatively bioactive polyphenolic compounds that, in most cases, have not been well characterised structurally. Non-extractable proanthocyanidins (NEPA) of a polymeric nature are part of the dietary fibre fraction of food. Using liquid chromatography coupled to a mass spectrometer equipped with an electrospray ionisation chamber and a triple quadrupole mass analyser for tandem analysis (HPLC–ESI–QqQ–MS/MS) techniques, we examine the phenolic metabolites present in urine and faeces from rats 24 h after ingestion of an NEPA-rich fraction. We show that NEPA are partially depolymerised during their transit along the intestinal tract, as evidenced by the presence of (epi)catechin (EC) monomers and dimers in faeces and phase II conjugates of EC in urine. Moreover, NEPA are further metabolised by the intestinal microbiota into smaller metabolites including phenolic acids that are present in urine as both free phenolics and conjugates with glucuronate or sulphate moieties. For the first time, we report evidence that NEPA behave in vivo as a source of phenolics that are released progressively and deliver phenolic species that come into contact with the intestinal walls and are bioavailable for at least 24 h after ingestion.

The present study was aimed to improve and simplify the 13C-mixed TAG (13C-MTG) breath test while keeping it acceptable for the patient. Healthy volunteers (ten women and eight men) were examined on four occasions, receiving in a random order 300 mg 13C-MTG: (1) contained in two wafers; (2) administered with a 50 g wheat roll; as well as given with either (3) 10 or (4) 30 g butter, spread onto a 50 g wheat roll, as the test meal, respectively. Samples of expiratory air were taken for 6 h postprandially for the mass spectroscopic measurement of 13CO2 enrichment. After intake of the sole 13C-MTG, the cumulative 13C recovery in breath air (AUC) appeared to be unsatisfactory, as after 6 h it did not exceed 10 %. Application of the substrate with the 50 g wheat roll did not bring about any improvement in this parameter. The addition of the unlabelled fat to the test meal dramatically increased the cumulative 13C recovery. However, we found higher values for the momentary 13C recovery and AUC with 10 g butter compared with 30 g. It can be concluded that: (1) addition of unlabelled fat is indispensable to obtain a proper course of the breath 13C elimination during the conduct of the 13C-MTG breath test and (2) it is possible to apply a considerably smaller amount of the unlabelled fat than has previously been recommended for this test.

Because of its high prevalence and implications for quality of life and possibly even disease progression, depression has been intensively studied in multiple sclerosis (MS) over the past 25 years. Despite the publication of numerous excellent empirical research papers on this topic during that time, the publication of theoretical work that attempts to explain depression in a comprehensive way is scarce. In this study, we present a theoretical model that attempts to integrate existing work on depression in MS and provide testable hypotheses for future work. The model suggests that risk for depression begins with the onset of MS. MS results in disease-related changes such as increased lesion burden/brain atrophy and immunological anomalies that are associated with depression in MS, but explain only a relatively limited proportion of the variance. Common sequelae of MS including fatigue, physical disability, cognitive dysfunction, and pain, have all been shown to have an inconsistent or relatively weak relationship to depression in the literature. In the model, we propose that four variables—social support, coping, conceptions of the self and illness, and stress—may moderate the relationship between the above common MS sequelae with depression and help to explain inconsistencies in the literature. (JINS, 2008, 14, 691–724.)

There is a growing literature examining working memory deficits using functional imaging and there has been great convergence in the findings, to date, but interpretations have varied. Investigators consistently observed recruitment of neural resources in clinical samples, with some examiners attributing these findings to neural inefficiency and others attributing differences to neural compensation and/or brain reorganization. It is the goal of this paper to address the current interpretation of altered brain activation in clinical imaging studies of working memory dysfunction with specific emphasis on findings in prefrontal cortex (PFC). Throughout this review, the methods used to examine brain reorganization associated with working memory dysfunction are critiqued with the goal of understanding how study design has influenced data interpretation. It is proposed that much of what has been considered “aberrant” neural activity is not indicative of neural compensation, as it has been typically defined, and does not represent brain reorganization. Instead, recruitment of neural resources in PFC can be explained by a natural, and largely overlooked, role of cognitive control in accommodating neural dysfunction secondary to brain injury and disease. This paper provides predictions based on this proposition and a critique of the current methods available for testing these predictions. (JINS, 2008, 14, 526–534.)

Information processing speed and episodic memory are two commonly affected cognitive abilities in MS. Insights into the mechanisms of and relationships between these abilities have recently come from structural neuroimaging techniques, but few studies have used fluid-attenuated inversion recovery (FLAIR), a neuroimaging sequence known to be sensitive to cortical and juxtacortical lesions in MS. We hypothesized that a volumetric index of FLAIR total lesion volume (TLV) would be associated with slowed processing speed and verbal memory dysfunction in MS. Twenty MS patients underwent FLAIR imaging and were administered measures of verbal memory and processing speed. Correlational and regression analyses indicated that TLV was directly and independently related to measures of processing speed and verbal memory, and TLV accounted for 56% of the variance in cognitive performance. These findings, considered in the context of prior work, suggest that FLAIR TLV is a useful predictor of commonly impaired cognitive functions in MS, and shows promise as a functionally relevant biomarker for disease status. (JINS, 2005, 11, 205–209.)

Inflammatory responses occur within tissue microenvironments, with functional contributions from both haematopoietic (lymphocytic) cells and stromal cells (including macrophages and fibroblasts). These environments are complex – a compound of many different cell types at different stages of activation and differentiation. Traditional models of inflammatory disease highlight the role of antigen-specific lymphocyte responses and attempt to identify causative agents. However, recent studies have indicated the importance of tissue microenvironments and the innate immune response in perpetuating the inflammatory process. The prominent role of stromal cells in the generation and maintenance of these environments has begun to challenge the primacy of the lymphocyte in regulating chronic inflammatory processes. Sensible enquiries into factors regulating the persistence of inflammatory disease necessitate an understanding of the mechanisms regulating tissue homeostasis and remodelling during inflammation. This article highlights recent insights into the factors regulating dynamic aspects of inflammation, focusing particularly on mononuclear cell infiltrates, their interactions with stromal cells in tissues and the relevance of these interactions to existing and possible future therapies. A key feature of current research has been a growing appreciation that disordered spatial and temporal interactions between infiltrating immune cells and resident stromal cells lie at the heart of disease persistence.

this qualitative study investigated multiple sclerosis (ms) patients' holistic experience of magnetic resonance imaging (mri). with support from the ms society, eight individuals with ms were interviewed using unstructured, tape-recorded interviews.

the holistic experience was overall a negative one. the most negative aspects being cited as the lack of support and information around the time of diagnosis. the loss of control felt by individuals was also an import ant issue, which led patients to pursue self-empowerment by actively seeking out information and support.

the study suggests improvement in information to patients attending for mri is essential, along with adequate support (including details about the ms society) being offered at the time of receiving confirmed diagnosis and results. the study shows that for some patients, there is a long lasting negative effect from the scan, which impacts on other activities, as well as affecting the patients' willingness to undergo future imaging.