Immunology taught by lung dendritic cells.

Dendritic cells (DCs) are leukocytes specialised in the uptake, processing, and presentation of antigen and fundamental in regulating both innate and adaptive immune functions. They are mainly localised at the interface between body surfaces and the environment, continuously scrutinising incoming antigen for the potential threat it may represent to the organism. In the respiratory tract, DCs constitute a tightly enmeshed network, with the most prominent populations localised in the epithelium of the conducting airways and lung parenchyma. Their unique localisation enables them to continuously assess inhaled antigen, either inducing tolerance to inoffensive substances, or initiating immunity against a potentially harmful pathogen. This immunological homeostasis requires stringent control mechanisms to protect the vital and fragile gaseous exchange barrier from unrestrained and damaging inflammation, or an exaggerated immune response to an innocuous allergen, such as in allergic asthma. During DC activation, there is upregulation of co-stimulatory molecules and maturation markers, enabling DC to activate naïve T cells. This activation is accompanied by chemokine and cytokine release that not only serves to amplify innate immune response, but also determines the type of effector T cell population generated. An increasing body of recent literature provides evidence that different DC subpopulations, such as myeloid DC (mDC) and plasmacytoid DC (pDC) in the lungs occupy a key position at the crossroads between tolerance and immunity. This review aims to provide the clinician and researcher with a summary of the latest insights into DC-mediated pulmonary immune regulation and its relevance for developing novel therapeutic strategies for various disease conditions such as infection, asthma, COPD, and fibrotic lung disease.

Différences régionales de l'incidence des fractures de la hanche dues à l'ostéoporose chez les femmes âgées : influence de la condition physique et de la nutrition

Résumé L'ostéoporose est une maladie systémique du squelette caractérisée par une fragilité osseuse augmentée avec pour conséquence une augmentation de la susceptibilité aux fractures. C'est actuellement un important problème de santé publique avec des conséquences majeures pour les systèmes de soins tant d'un point de vue médical que financier. Les projections mondiales prévoient une augmentation significative du nombre de fractures de la hanche d'ici 2050. Cette étude vise à analyser l'influence des apports nutritionnels par rapport à celle de la condition physique sur le risque de fracture ostéoporotique en reprenant les données évaluant la consommation de produits laitiers au sein du collectif de l'étude SEMOF («Evaluation suisse de méthodes de mesure du risque de fracture ostéoporotique»). Nous avons d'abord montré que les apports moyens en calcium des 7788 femmes âgées de 70 ans et plus ayant participé à l'étude sont inférieurs aux recommandations suisses et internationales. Des trois régions étudiées, la Suisse romande est celle où les apports quotidiens moyens en calcium et en protéines provenant des produits laitiers sont les plus faibles et où l'incidence des fractures de la hanche secondaires à l'ostéoporose est la plus élevée. Les apports en calcium et en protéines sont également plus élevés à la campagne par rapport à la ville alors que l'incidence des fractures de la hanche n'est pas significativement différente entre ville et campagne. De plus, nous avons montré que les apports quotidiens moyens en calcium et en protéines provenant des produits laitiers ne diffèrent pas significativement entre les femmes avec ou sans fracture de la hanche pendant le suivi. En revanche, la condition physique des femmes qui ont présenté une fracture de la hanche est significativement moins bonne. Sur la base de données anamnestiques concernant les facteurs de risque de chute et la mobilité, nous avons développé un score permettant d'identifier les femmes les plus à risque de chute. La condition physique de ces femmes, attestée par le test de la chaise et la mesure de la force de préhension est la moins bonne. Toutefois, leurs apports quotidiens moyens en calcium et en protéines provenant des produits laitiers ne diffèrent pas significativement par rapport aux femmes à faible risque de chute. En conclusion, le risque de fracture de la hanche liée à l'ostéoporose est plus élevé chez les femmes de plus de 70 ans vivant en Suisse romande que dans les deux autres régions linguistiques. Il est déterminé avant tout par le risque de chute et par la condition physique. Les apports en calcium et en protéines provenant des produits laitiers, tels que nous les avons évalués ne semblent pas déterminants.

Vitamin C requirements in parenteral nutrition.

Some biochemical functions of vitamin C make it an essential component of parenteral nutrition (PN) and an important therapeutic supplement in other acute conditions. Ascorbic acid is a strong aqueous antioxidant and is a cofactor for several enzymes. The average body pool of vitamin C is 1.5 g, of which 3%-4% (40-60 mg) is used daily. Steady state is maintained with 60 mg/d in nonsmokers and 140 mg/d in smokers. Shocked surgical, trauma, and septic patients have a drastic reduction of circulating plasma ascorbate concentrations. These low concentrations require 3-g doses/d to restore normal plasma ascorbate concentrations, questioning the recommended PN dose of 100 mg/d. Determination of intravenous requirements is usually based on plasma concentrations, which are altered during the inflammatory response. There is no clear indicator of deficiency: serum or plasma ascorbate concentrations <0.3 mg/dL (20 micromol/L) indicates inadequate vitamin C status. On the basis of available pharmacokinetic data the 100 mg/d dose for patients receiving home PN and 200 mg/d for stable adult patients receiving PN are adequate, but requirements have been shown to be higher in perioperative, trauma, burn, and critically ill patients, paralleling oxidative stress. One recommendation cannot fit all categories of patients. Large vitamin C supplements may be considered in severe critical illness, major trauma, and burns because of increased requirements resulting from oxidative stress and wound healing. Future research should distinguish therapeutic use of high-dose ascorbic acid antioxidant therapy from nutritional PN requirements.

Allergo-immunologie. 1. Nouveautés dans le traitement des crises aiguës d'angioedème héréditaire [Allergy-immunology. New therapies for acute attacks in hereditary angioedema].

Hereditary angioedema is a disease which develops as a result of a deficiency or dysfonction of C1-inhibitor, a key regulator of the complement, coagulation and contact cascades, resulting among others in excessive release of bradykinin. This disease mortality rate is high in absence of immediate and effective treatment, in particular in presence of acute attacks of the upper respiratory tract (laryngeal edema). Until now only administration of a purified C1-inhibitor extract was effective against these symptoms. This paper aims to synthesise essentials knowledge concerning news drugs, in particular icatibant, a selective bradykinin B2- receptor antagonist whose use should be widened to the treatment of angioedema with ACE-inhibitors intolerance.

A festschrift for Roland L. Weinsier: nutrition scientist, educator, and clinician.

Roland L. Weinsier, M.D., Dr.P.H., devoted himself to the fields of nutrition and obesity for more than 35 years. He contributed outstanding work related to the treatment of obesity through dietary and lifestyle change; metabolic/energetic influences on obesity, weight loss, and weight regain; body composition changes accompanying weight loss and regain; the health benefits and risks of weight loss; nutrition education for physicians; and nutrition support of sick patients. He served on the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) National Task Force on Prevention and Treatment of Obesity, as Chair of the University of Alabama at Birmingham's Department of Nutrition Sciences, and as Founder and Director of its NIDDK-funded Clinical Nutrition Research Center. He was a long-time and active member of NAASO, serving in the roles of Councilor, Publications Committee Chair, Continuing Medical Education Course Director, Public Relations Committee Chair, and Membership Committee Co-Chair, to name just a few. He was well respected as a staunch defender of NAASO's scientific integrity in these roles. Sadly, Roland Weinsier died on November 27, 2002. He will be missed and remembered by many as a revered and beloved teacher, mentor, healer, and scholar.

Parenteral nutrition in the intensive care unit: cautious use improves outcome.

Critical illness is characterised by nutritional and metabolic disorders, resulting in increased muscle catabolism, fat-free mass loss, and hyperglycaemia. The objective of the nutritional support is to limit fat-free mass loss, which has negative consequences on clinical outcome and recovery. Early enteral nutrition is recommended by current guidelines as the first choice feeding route in ICU patients. However, enteral nutrition alone is frequently associated with insufficient coverage of the energy requirements, and subsequently energy deficit is correlated to worsened clinical outcome. Controlled trials have demonstrated that, in case of failure or contraindications to full enteral nutrition, parenteral nutrition administration on top of insufficient enteral nutrition within the first four days after admission could improve the clinical outcome, and may attenuate fat-free mass loss. Parenteral nutrition is cautious if all-in-one solutions are used, glycaemia controlled, and overnutrition avoided. Conversely, the systematic use of parenteral nutrition in the ICU patients without clear indication is not recommended during the first 48 hours. Specific methods, such as thigh ultra-sound imaging, 3rd lumbar vertebra-targeted computerised tomography and bioimpedance electrical analysis, may be helpful in the future to monitor fat-free mass during the ICU stay. Clinical studies are warranted to demonstrate whether an optimal nutritional management during the ICU stay promotes muscle mass and function, the recovery after critical illness and reduces the overall costs.

Hochkalorische Ernährung bei chronischer obstruktiver Lungenkrankheit [High-caloric nutrition in chronic obstructive lung disease]

A body weight lower than 90% of the optional value has an unfavorable influence on the prognosis of chronic obstructive pulmonary disease (COPD). Short term studies of up to three months duration have shown improved function of respiratory muscle exercise tolerance and immunologic parameters by an increased caloric intake of 45 kcal/kg body weight. In a randomized trial of twelve months 14 of 30 patients with an average FEV1 of 0.8 l were instructed to take a high calorie diet. For simplicity a part of the calories were administered as Fresubin, a fluid nutrient formula. Although a weight gain of 7 kg (p = 0.003) was obtained the difference to the control group was statistically not significant (p = 0.08). The same was true for skin fold thickness (12.4 vs 5.7 mm), change of ventilatory parameters and the 6 minute walking distance (-33 vs -86 m). Subjective improvement was, however, impressive in all patients with dietary intervention, explainable probably by increased attention. Dietary counselling for increased intake of calories, vitamins and also calcium is thus very important in the treatment of patients with COPD.

Nutrition parentérale compé- mentaire de la nutrition entérale aux soins intensifs: une association logique [Supplemental parenteral nutrition for intensive care patients: a logical combination with enteral nutrition]

Undernutrition is a widespread problem in the intensive care and is associated with a worse clinical outcome. Enteral nutrition is the recommended nutritional support in ICU patients. However, enteral nutrition is frequently insufficient to cover protein-energy needs. The initiation of supplemental parenteral nutrition, when enteral nutrition is insufficient, could optimize the nutritional therapy. Such a combination could allow reducing morbidity, length of stay and recovery, as well as improving quality of life and health care costs. Prospective studies are currently underway to test this hypothesis.

Influence of nutrition on urinary oxalate and calcium in preterm and term infants.

Few data for normal urinary oxalate (Ox) and calcium (Ca) excretion related both to gestational age and nutritional factors have been reported in preterm or term infants. We therefore determined the molar Ox and Ca to creatinine (Cr) ratios in spot urines from 64 preterm and 37 term infants aged 1-60 days, either fed formula or human milk (HM). Only vitamin D was supplemented; renal or metabolic diseases were excluded. Urinary Ox/Cr ratio was higher in preterm than in term infants, both when formula fed (1st month 253 vs. 180 mmol/mol and 2nd month 306 vs. 212 mmol/mol; P&lt;0.05) or HM fed (206 vs. 169 mmol/ mol and 283* vs. 232 mmol/mol; *P&lt;0.05). Ox/Cr was also higher in formula- than HM-fed preterm infants. The ratio increased during the first 2 months of life irrespective of nutrition. Urinary Ca/Cr ratio was comparable in all groups during the 1st month of life, except for a lower (P &lt; 0.05) value in term infants fed HM (0.10 mol/mol). It increased in all groups during the 2nd month of life, being highest in HM-fed preterm infants (1.86 mol/mol). In conclusion, urinary Ox and Ca excretion is influenced by both gestational age and nutrient intake in preterm and term infants.

The mycorrhizal contribution to plant productivity, plant nutrition and soil structure in experimental grassland.

Previous studies have shown that arbuscular mycorrhizal fungi (AMF) can influence plant diversity and ecosystem productivity. However, little is known about the effects of AMF and different AMF taxa on other important community properties such as nutrient acquisition, plant survival and soil structure. We established experimental grassland microcosms and tested the impact of AMF and of different AMF taxa on a number of grassland characteristics. We also tested whether plant species benefited from the same or different AMF taxa in subsequent growing seasons. AMF enhanced phosphorus acquisition, soil aggregation and survival of several plant species, but AMF did not increase total plant productivity. Moreover, AMF increased nitrogen acquisition by some plant species, but AMF had no effect on total N uptake by the plant community. Plant growth responses to AMF were temporally variable and some plant species obtained the highest biomass with different AMF in different years. Hence the results indicate that it may be beneficial for a plant to be colonized by different AMF taxa in different seasons. This study shows that AMF play a key role in grassland by improving plant nutrition and soil structure, and by regulating the make-up of the plant community.

Invader immunology: invasion history alters immune system function in cane toads (Rhinella marina) in tropical Australia.

Because an individual's investment into the immune system may modify its dispersal rate, immune function may evolve rapidly in an invader. We collected cane toads (Rhinella marina) from sites spanning their 75-year invasion history in Australia, bred them, and raised their progeny in standard conditions. Evolved shifts in immune function should manifest as differences in immune responses among the progeny of parents collected in different locations. Parental location did not affect the offspring's cell-mediated immune response or stress response, but blood from the offspring of invasion-front toads had more neutrophils, and was more effective at phagocytosis and killing bacteria. These latter measures of immune function are negatively correlated with rate of dispersal in free-ranging toads. Our results suggest that the invasion of tropical Australia by cane toads has resulted in rapid genetically based compensatory shifts in the aspects of immune responses that are most compromised by the rigours of long-distance dispersal.