Renata Ramalho

Tachykinin receptors antagonism for asthma: a systematic review

BackgroundTachykinins substance P, neurokinin A and neurokinin B seem to account for asthma pathophysiology by mediating neurogenic inflammation and several aspects of lung mechanics. These neuropeptides act mainly by their receptors NK1, NK2 and NK3, respectively which may be targets for new asthma therapy.MethodsThis review systematically examines randomized controlled trials evaluating the effect of tachykinins receptors antagonism on asthma. Symptoms, airway inflammation, lung function and airway inflammation were considered as outcomes. We searched the Cochrane Airways Group Specialized Register of Asthma Trials, Cochrane Database of Systematic Reviews, MEDLINE/PubMed and EMBASE. The search is as current as June 2010. Quality rating of included studies followed the Cochrane Collaboration and GRADE Profiler approaches. However, data were not pooled together due to different measures among the studies.ResultsOur systematic review showed the potential of NK receptor antagonist to decrease airway responsiveness and to improve lung function. However, effects on airway inflammation and asthma symptoms were poorly or not described.ConclusionThe limited available evidence suggests that tachykinin receptors antagonists may decrease airway responsiveness and improve lung function in patients with asthma. Further large randomized trials are still required.

Substance P antagonist improves both obesity and asthma in a mouse model

Evidence suggests a causal relationship between obesity and asthma; however, the underlying mechanisms remain unknown. Substance P (SP), involved in neurogenic inflammation by acting through its receptor NK1‐R, seems to participate in obese–asthma phenotype in mice.

Use of a common food frequency questionnaire (FFQ) to assess dietary patterns and their relation to allergy and asthma in Europe: pilot study of the GA2LEN FFQ.

Background/Objectives:Comparable international data on food and nutrient intake is often hindered by the lack of a common instrument to assess food intake. The objective of this study was within the Global Allergy and Asthma European Network of Excellence (GA2LEN), we developed and piloted a food frequency questionnaire (FFQ) to assess its validity in Europe.Subjects/Methods:Five countries participating in GA2LEN took part in the pilot study. A total of 200 adults aged 31–75 years were invited to complete a FFQ in two occasions and to give a blood sample. The intra-class correlation coefficient (ICC) was used to assess repeatability of the FFQ. Plasma phospholipid fatty acids (FAs) were analysed by gas chromatography. Pearson correlation was used to analyse the correlation between estimated dietary FA intake and plasma phospholipid FA levels.Results:A total of 177 participants (89%) had complete data on FFQ1 and plasma phospholipid FAs. In all, 152 participants (76%) completed both FFQs. ICCs between macronutrients ranged from 0.70 (saturated FAs) to 0.78 (proteins) and between 0.70 (retinol) and 0.81 (vitamin D) for micronutrients. Dietary n-3 FAs showed a good correlation with total plasma phospholipid n-3 FAs and with docosahexaenoic acid in the whole sample (0.40) and in individual countries. Poor correlations were observed for other FAs.Conclusions:The GA2LEN FFQ is an appropriate tool to estimate dietary intake for a range of nutrients across Europe regardless of cultural and linguistic differences. The FFQ seems to be useful to estimate the intake of n-3 FAs but not other FAs.

Neurogenic inflammation in allergen-challenged obese mice: a missing link in the obesity-asthma association?

ABSTRACT Aim: A number of studies have shown an association between obesity and asthma. Controversy remains on the mechanisms supporting this association. In this study we aimed to assess neurogenic inflammation in a model of diet-induced obesity and allergen-challenged mice. Methods: High fat diet-induced (HFD) obese Balb/c mice were sensitized and challenged with ovalbumin (OVA). Glucose, insulin, OVA-specific IgE and substance P (SP), and the main tachykinin involved in neurogenic inflammation, were quantified in sera. Cell counts were performed in bronchoalveolar lavage fluid (BALF). The extent of peribronchial infiltrates was estimated on lung tissue sections and inflammation was score based on inflammatory cell counts surrounding the bronchi. Results: Obesity per se and allergen-sensitization per se increased serum SP (P = .027, P = .004, respectively). Further increased was observed in obese-sensitized mice (P = .007). Obese-sensitized mice also showed higher insulin (P = .0016), OVA-specific IgE (P = .016), peribronchial inflammatory score (P = .045), and tendency for higher glycemia. The interaction of obesity and asthma on SP levels was confirmed (P = .005, R2 = 0.710). SP was positively correlated with metabolic (glycemia, r = 0.539, P = .007) and allergic inflammation parameters (BALF eosinophils, r = 0.445, P = 0.033; BALF mast cells, r = 0.574, P = .004; peribronchial inflammation score, r = 0.661, P < .001; and OVA-specific IgE, r = 0.714, P < .001). Conclusions: Our findings provide support to the neurogenic inflammation link between obesity and asthma in mice. These two conditions independently increased SP and the presence of both pathologies further increased this level. Neurogenic inflammation may be a previously unrecognized mechanism beyond the obese-asthma phenotype. Further studies are need to confirm this role of SP in human obesity-asthma association.

Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotype

AIMS Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obese-allergen sensitized mice. MAIN METHODS Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1+) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression. KEY FINDINGS Obesity and allergen-sensitization together increased the number of LYVE-1+ lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues. SIGNIFICANCE The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.

Prognostic value of unrelated atypical serum immunofixation patterns during Multiple Myeloma therapy

Autologous stem cell transplantation (ASCT) is the gold standard therapy for suitable multiple myeloma (MM) patients after induction with high dose therapy. To date, the evidence of a reliable marker of prognosis in these cases remains scarce. Our aim was to evaluate appearance of unrelated atypical serum immunofixation patterns (ASIPs) as a marker of prognosis in MM patients submitted to ASCT. We retrospectively analysed data from 65 patients. Interestingly, we observed that presence of ASIPs was associated with longer progression-free survival and longer overall survival. Our results suggested that presence of ASIPs could be a novel marker of good prognosis in MM patients submitted to ASCT.

Omega-3 therapeutic supplementation in a patient with metastatic adenocarcinoma of the pancreas with muscle mass depletion

Pancreatic adenocarcinoma has an extremely poor prognosis. With the best available treatments, the median overall survival duration is still less than 1 year. Most patients develop anorexia and major muscle mass loss that interfere with chemotherapy tolerance and survival. In this paper, we present a case in which these problems were a major concern. A multidisciplinary approach with chemotherapy and close nutritional support permitted better control of the disease and longer survival. We also review the literature on nutritional interventions that show an improvement in quality of life and survival in these patients.

Adverse effect of a nutritional supplement for hair loss

ejd.2010.1249 Auteur(s) : Renata RAMALHO1,2 rrenata@med.up.pt, Osvaldo CORREIA1,2, Luis DELGADO1 1 Faculty of Medicine, Department of Immunology, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal 2 Centro de Dermatologia Epidermis, Instituto CUF, Matosinhos, Portugal The rationale for considering nutritional supplements as a complementary treatment for hair loss is based on the fact that selective nutrients can improve hair and scalp health. For hair loss, a wide range of different supplements, [...]

Immunosenescence and nutrition: reviewing clinical evidence on pre-, pro- and synbiotics in aging

Aging is considered a complex process, characterized by a general decline in physiological functions, as well as increased morbidity and mortality. Being old, healthy and autonomous for the daily life constitute the hallmark of successful aging. However, dependency and frailty are common to people aged 65 or older. The aging process in accompanied by altered immune responsiveness, both at the adaptive and innate levels, that are correlated to malnutrition and frailty. Immunosenescence is also a contributor for increase susceptibility to infections and to vaccination resistance in the elderly. The impact of aging in mucosal immunity or mucosal immunosenescence has gained the interest of researchers in recent years. Mucosal immune response is impaired in elderly, probably adding a contribution to reduced vaccination efficacy and increased susceptibility to infection. The impact of aging on mucosal immunity may indicate a possible role of therapeutic modulation of mucosal immunosenescence by pre-, probiotics and synbiotics. In this review, the author gathered the most relevant clinical evidence regarding the effect of pre-, proand synbiotics in innate and adaptive immune responses of people aged 65 or older. The concepts and immunological features of immunosenescence and mucosal immunosenescence were also carefully reviewed. Correspondence to: Renata Ramalho, Instituto Superior de Ciências da Saúde Egas Moniz, Campus Universitário Quinta da Granja, 2829 – 511 Monte de Caparica, Portugal, Email: rramalho@egasmoniz.edu.pt