Diet and Systemic Lupus Erythematosus (SLE): From Supplementation to Intervention.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterised by immune dysregulation affecting multiple organs. Current anti-inflammatory treatments used in SLE are associated with unwanted side-effects. Dietary supplementation has been suggested as a safe and effective addition to conventional treatment, but evidence of efficacy in SLE or preventing associated comorbidities is uncertain. METHODS: We identified literature on clinical trials focused on nutritional interventions in SLE aiming to improve inflammation and comorbidities. A systematic-type search on Embase, Medline, and the Cochrane Library, was conducted to identify nutritional interventions among SLE patients in the past 15 years that met our inclusion criteria. RESULTS: We identified 2754 articles, of which 14 were eligible for inclusion based on our set criteria and were subsequently quality assessed. Vitamin D or E supplementation was associated with respective improvement of inflammatory markers or antibody production, but not disease activity scores in most studies. Despite their expected synergistic actions, the addition of curcumin on vitamin D supplementation had no additional effects on disease activity or inflammatory markers. Trials of omega-3 fatty acid supplementation presented significant reductions in ESR, CRP, disease activity, inflammatory markers, and oxidative stress, and improved lipid levels and endothelial function, while a low glycaemic index (GI) diet showed evidence of reduced weight and improved fatigue in patients. CONCLUSIONS: Different dietary guidelines can therefore be implicated to target specific SLE symptoms or therapeutic side-effects. This systematic review highlights the scarcity of larger and longer in duration trials with homogenous methodologies and verifiable outcomes to assess disease progression.

The Interplay between Housing Environmental Attributes and Design Exposures and Psychoneuroimmunology Profile-An Exploratory Review and Analysis Paper in the Cancer Survivors' Mental Health Morbidity Context.

Adult cancer survivors have an increased prevalence of mental health comorbidities and other adverse late-effects interdependent with mental illness outcomes compared with the general population. Coronavirus Disease 2019 (COVID-19) heralds an era of renewed call for actions to identify sustainable modalities to facilitate the constructs of cancer survivorship care and health care delivery through physiological supportive domestic spaces. Building on the concept of therapeutic architecture, psychoneuroimmunology (PNI) indicators-with the central role in low-grade systemic inflammation-are associated with major psychiatric disorders and late effects of post-cancer treatment. Immune disturbances might mediate the effects of environmental determinants on behaviour and mental disorders. Whilst attention is paid to the non-objective measurements for examining the home environmental domains and mental health outcomes, little is gathered about the multidimensional effects on physiological responses. This exploratory review presents a first analysis of how addressing the PNI outcomes serves as a catalyst for therapeutic housing research. We argue the crucial component of housing in supporting the sustainable primary care and public health-based cancer survivorship care model, particularly in the psychopathology context. Ultimately, we illustrate a series of interventions aiming at how housing environmental attributes can trigger PNI profile changes and discuss the potential implications in the non-pharmacological treatment of cancer survivors and patients with mental morbidities.

The IHAT-GUT Iron Supplementation Trial in Rural Gambia: Barriers, Facilitators, and Benefits.

INTRODUCTION: In most sub-Saharan African countries iron deficiency anaemia remains highly prevalent in children and this has not changed in the last 25 years. Supplementation with iron hydroxide adipate tartrate (IHAT) was being investigated in anaemic children in a phase two clinical trial (termed IHAT-GUT), conducted at the Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine (LSHTM) (abbreviated as MRCG hereof). This qualitative study aimed to explore the personal perceptions of the trial staff in relation to conducting a clinical trial in such settings in order to highlight the health system specific needs and strengths in the rural, resource-poor setting of the Upper River Region in the Gambia. METHODS: Individual interviews (n = 17) were conducted with local trial staff of the IHAT-GUT trial. Data were analysed using inductive thematic analysis. RESULTS: Potential barriers and facilitators to conducting this clinical trial were identified at the patient, staff, and trial management levels. Several challenges, such as the rural location and cultural context, were identified but noted as not being long-term inhibitors. Participants believed the facilitators and benefits outnumbered the barriers, and included the impact on education and healthcare, the ambitious and knowledgeable locally recruited staff, and the local partnership. CONCLUSIONS: While facilitators and barriers were identified to conducting this clinical trial in a rural, resource-poor setting, the overall impact was perceived as beneficial, and this study is a useful example of community involvement and partnership for further health improvement programs. To effectively implement a nutrition intervention, the local health systems and context must be carefully considered through qualitative research beforehand.

Iron deficiency anaemia: experiences and challenges.

Iron deficiency remains the largest nutritional deficiency worldwide and the main cause of anaemia. Severe iron deficiency leads to anaemia known as iron deficiency anaemia (IDA), which affects a total of 1·24 billion people, the majority of whom are children and women from resource-poor countries. In sub-Saharan Africa, iron deficiency is frequently exacerbated by concomitant parasitic and bacterial infections and contributes to over 120 000 maternal deaths a year, while it irreparably limits the cognitive development of children and leads to poor outcomes in pregnancy.Currently available iron compounds are cheap and readily available, but constitute a non-physiological approach to providing iron that leads to significant side effects. Consequently, iron deficiency and IDA remain without an effective treatment, particularly in populations with high burden of infectious diseases. So far, despite considerable investment in the past 25 years in nutrition interventions with iron supplementation and fortification, we have been unable to significantly decrease the burden of this disease in resource-poor countries.If we are to eliminate this condition in the future, it is imperative to look beyond the strategies used until now and we should make an effort to combine community engagement and social science approaches to optimise supplementation and fortification programmes.

Attenuation of alpha-adrenergic-induced vasoconstriction by dietary wild blueberries (Vaccinium angustifolium) is mediated by the NO-cGMP pathway in spontaneously hypertensive rats (SHRs).

The role of wild blueberries (WB) on key signaling steps of nitric oxide (NO) and cyclooxygenase (COX) pathways was examined in spontaneously hypertensive rats (SHRs) after eight weeks on a control (C) or an 8% w/w WB diet. Aortic rings from SHRs were stimulated with phenylephrine (Phe) in the absence or presence of inhibitors of: soluble guanylyl cyclase (sGC), phosphodiesterase-5 (PDE(5)), prostaglandin I(2) (PGI(2)) synthase and thromboxane A(2) (TXA(2)) synthase. Additionally, enzymatic activities in these pathways were determined by the concentration of NO, cyclic guanosine monophosphate (cGMP), PGI(2) and TXA(2). In the WB-fed SHR, attenuation of Phe-induced vasoconstriction was mediated by an increased synthesis or preservation of cGMP. Despite an increased release of PGI(2) in the WB group, neither inhibition of PGI(2) or TXA(2) synthase resulted in a different response to Phe between the control and the WB rings. Hence, in the SHR, WB decrease Phe-mediated vasoconstriction under basal conditions by enhancing NO-cGMP signaling without a significant involvement of the COX pathway.

A wild blueberry-enriched diet (Vaccinium angustifolium) improves vascular tone in the adult spontaneously hypertensive rat.

The effect of a wild blueberry-enriched diet on vasoconstriction and vasorelaxation was examined in the adult, 20-week-old spontaneously hypertensive rat (SHR) after 8 weeks of a control (C) or an 8% wild blueberry (WB) diet. Nitric oxide (NO)- and cyclooxygenase (COX)-mediated aortic responses were examined ex vivo with the agonists L-phenylephrine (Phe) and acetylcholine (Ach), in the absence or presence of the NO synthase (NOS) inhibitor L-NG-monomethyl arginine (L-NMMA) or the COX inhibitor mefenamic acid (MFA). The vasoconstriction elicited by Phe was reduced in the WB group, attributed to the NO pathway, favoring a lower vascular tone under basal conditions. Acetylcholine-induced vasorelaxation in the WB group was possibly mediated through the COX, but not the NO pathway. These findings document the potential of wild blueberries to modify major pathways of vasomotor control and improve the vascular tone in the adult SHR with endothelial dysfunction.

Vascular reactivity is affected by dietary consumption of wild blueberries in the Sprague-Dawley rat.

We have previously reported that consumption of blueberry-enriched (BB) diets attenuates the arterial contractile response to alpha(1)-adrenergic stimuli and affects vasomotor tone via endothelium-related pathways. The present study was designed to evaluate vascular function and responsiveness in aortas of weanling male Sprague-Dawley rats fed a control (C) or a BB diet for 7 weeks. Vascular ring studies were conducted in 3-mm isolated rat aortic ring preparations to investigate vasoconstriction induced by L-phenylephrine (Phe) (10(-8)-3 x 10(-6) M) and vasorelaxation induced by acetylcholine (ACh) (10(-8)-3 x 10(-6) M). Agonists were used alone and in the presence of nitric oxide (NO) synthase and cyclooxygenase (COX) inhibitors. We observed a significantly diminished vasoconstrictor response to Phe in aortic rings from rats fed the BB diet. Inhibition of NO synthase but not COX caused a significant increase in the constrictor response in both dietary groups, with the BB group having the greater response. Similarly, the participation of the NO pathway in endothelium-dependent vasorelaxation induced by ACh was greater in the rats fed a BB diet, while COX inhibition showed no effect on maximum ACh-induced vasorelaxation in any diet group. The vessel sensitivity of BB aortic rings to the vasoconstrictor and vasodilator was significantly reduced when compared to controls. We have concluded that diets enriched with blueberries, fed for 7 weeks in Sprague-Dawley rats, seem to affect NO metabolic pathways in the aorta at basal and stimulated levels.

Dietary manganese affects the concentration, composition and sulfation pattern of heparan sulfate glycosaminoglycans in Sprague-Dawley rat aorta.

We examined the effect of dietary Mn on the composition and structure of heparan sulfate (HS) glycosaminoglycans (GAGs) of rat aorta. Animals were randomly assigned to either a Mn deficient (MnD), adequate (MnA) or supplemented (MnS) diet (Mn<1, 10-15 and 45-50 ppm, respectively). After 15 weeks, aortic tissue GAGs were isolated with papain digestion, alkaline borohydride treatment and anion-exchange chromatography. Cellulose acetate electrophoresis and treatment of the fractions with specific lyases revealed the presence of three GAG populations, i.e. hyaluronan (HA), heparan sulfate (HS) and galactosaminoglycans (GalAGs). Disaccharide composition of the HS fractions was determined by HPCE following treatment with heparin lyases I, II and III. In MnS aortas we observed increased concentration of total GalAGs and decreased concentration of HS and HA, when compared to MnA aortas. Aortas from MnD and MnA rats appeared to have similar distribution of individual GAGs. Heparan sulfate chains of MnS aortas contained higher (41%) concentration of non-sulfated units compared to MnA ones. Variable amounts of trisulfated and disulfated units were found only in MnD and MnA groups but not in MnS. Our results demonstrate that HS biosynthesis in the rat aorta undergoes marked structural modifications that depend upon dietary Mn intake. The reduced expression and undersulfation of HSPGs with Mn supplementation might indicate a reduced ability of vascular cells to interact with biologically active molecules such as growth factors. Alterations in cell-membrane binding ability to a variety of extracellular ligands might affect signal-transduction pathways and arterial functional properties.

Wild blueberry-rich diets affect the contractile machinery of the vascular smooth muscle in the Sprague-Dawley rat.

Weanling male Sprague-Dawley rats were randomly fed a control diet (AIN-93) (C) or a blueberry diet (B) for 13 weeks, or a reverse diet (R) (C diet for 13 weeks, switched to the B diet for 8 weeks). Aortas were excised, and two intact and two endothelium-denuded rings were immersed in tissue baths containing physiological salt solution at 37 degrees C and aerated with 95% O(2) and 5% CO(2) (pH 7.4). Following equilibration and preconditioning under 1.5-g preload, cumulative dose-response curves were generated with six doses of the alpha1-adrenergic receptor-selective agonist L-phenylephrine (L-Phe, 10(8)-3 x 10(-6) M) and relaxed with one dose of acetylcholine (3 x 10(-6) M) to assess intact endothelium. The maximum force of contraction (Fmax) and vessel sensitivity (pD(2)) were determined in intact and endothelium-denuded rings. A two-way analysis of variance test revealed that blueberry-fed animals (B and R diets) developed a significantly lower F (max) (0.873 +/- 0.0463 and 0.9266 +/- 0.0463 g, respectively) when contracted with L-Phe, compared with the animals on the C diet (1.109 +/- 0.0463 g) (P < .05). The pD(2) of the intact rings was not significantly different among diet groups. Additionally, diet did not significantly affect the mean F (max) or pD(2) of endothelium-denuded rings. Our results indicate for the first time that wild blueberries incorporated into the diet affect the vascular smooth muscle contractile machinery by suppressing the alpha1-adrenergic receptor agonist-mediated contraction while having no effect on membrane sensitivity of the endothelial or vascular smooth muscle cell layer. Furthermore, their mechanism of action seems to be accomplished through an endothelium-dependent pathway.

Dietary manganese suppresses alpha1 adrenergic receptor-mediated vascular contraction.

We examined the effect of dietary manganese (Mn) on the vascular contractile machinery in rat thoracic aortas. Weanling male Sprague-Dawley rats were fed either an Mn-deficient (MnD), Mn-adequate (MnA) or Mn-supplemented (MnS) diet (<1, 10-15 and 45-50 ppm Mn, respectively). After 15 weeks on the diets the rats were sacrificed and 3-mm aortic rings were contracted in six cumulative doses of the alpha(1) adrenergic receptor agonist L-phenylephrine (l-Phe, 10(-8) to 3 x 10(-6) M) under 1.5-g preload and relaxed with one dose of acetylcholine (3 x 10(-6) M) to assess intact endothelium. The maximal force (F(max)) of contraction and relaxation, as well as the vessel sensitivity (pD(2)) were determined. Manganese deficiency, assessed by hepatic Mn content, significantly lowered the rate of animal growth. A two-way analysis of variance revealed that MnS animals developed lower F(max) when contracted with L-Phe compared with the MnD and MnA animals (P