Impaired growth and fertility of cAMP-specific phosphodiesterase PDE4D-deficient mice

In eukaryotic cells, the inactivation of the cyclic nucleotide signal depends on a complex array of cyclic nucleotide phosphodiesterases (PDEs). Although it has been established that multiple PDE isoenzymes with distinct catalytic properties and regulations coexist in the same cell, the physiological significance of this remarkable complexity is poorly understood. To examine the role of a PDE in cAMP signaling in vivo, we have inactivated the type 4 cAMP-specific PDE (PDE4D) gene, a mammalian homologue of the Drosophila dunce. This isoenzyme is involved in feedback regulation of cAMP levels. Mice deficient in PDE4D exhibit delayed growth as well as reduced viability and female fertility. The decrease in fertility of the null female is caused by impaired ovulation and diminished sensitivity of the granulosa cells to gonadotropins. These pleiotropic phenotypes demonstrate that PDE4D plays a critical role in cAMP signaling and that the activity of this isoenzyme is required for the regulation of growth and fertility.     

Potential therapeutic use of IL-37: a key suppressor of innate immunity and allergic immune responses mediated by mast cells

The host response to either exogenous or endogenous insults produces a series of changes, characterized by alterations in immunological functions and generation of mediators called cytokines which include the interleukin-1 (IL-1) family members. IL-1 acts as a hormone mediating the host responses to infection and inflammation. Blocking inflammatory IL-1 family members can be effective against inflammatory disorders, including allergies. IL-37, (formerly IL-1 family member 7), emerges as an inhibitor of innate and adaptive immunity by reducing circulating and organ cytokine levels. IL-37, mainly expressed in dendritic cells, monocytes, and plasma cells after TIR ligand activation, inhibits inflammatory cytokines and augments the level of anti-inflammatory IL-10. IL-37 is involved in allergic reaction and its expression in dendritic cells causes tollerogenicity and inhibits inflammatory response. Mast cells (MCs) are ubiquitous in the body, reside in numerous mucosal tissues, and are mediators of allergic reaction, and innate and adaptive immunity. MCs are important regulators of cytokine generation in the course of inflammatory responses and allergy, and are implicated in the pathophysiology of allergic asthma. Cysteine protease caspase-1 activation leads to the cleavage of pro-form of IL-1 into active mature IL-1 which is present in stimulated and unstimulated inflammatory MCs. Inflammatory cytokine inhibition, along with the augmentation of anti-inflammatory IL-10 by IL-37, is certainly beneficial and improves the pathogenesis of allergic disorders. However, in these studies, the exact mechanism(s) of IL-37-induced anti-inflammatory and anti-allergic activity along with its side effect(s) remain to be determined.     

Pulmonary embolism in pregnancy

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during pregnancy or early after delivery, remaining a diagnostic and therapeutic challenge in both states. The absolute incidence of pregnancy-associated VTE has been reported as 1 in 1,000 to 1 in 2,000 deliveries. With 5–6 million new births computed in Europe in 2010, the potential clinical relevance of diagnosing and treating gravidic VTE is immediately evident. Fivefold higher in a pregnant as compared with a non-pregnant woman, VTE risk is also higher in postpartum than antepartum period. Ranked absolute and relative thrombotic risk may be described in the several thrombophilic conditions experienced by women at risk, according to which specific prophylactic and therapeutic recommendations have been formulated by recent guidelines. The main purpose of the present review article was to emphasize the most recent findings and recommendations in diagnostic strategies, discussing thrombophilic risk evaluation, as well as risks and benefits of various diagnostic techniques for both mother and fetus.     

Rescue treatment for noninvasive ventilation failure due to interface intolerance with remifentanil analgosedation: a pilot study

Purpose  

To assess the feasibility of remifentanil-based sedation in hypoxemic acute respiratory failure (HARF) patients refusing to continue noninvasive ventilation (NPPV) for intolerance to two different interfaces—helmet and total face mask.     

Oxygen Therapy–Use and Abuse in Acute Myocardial Infarction Patients

In August 2008, an article was published in Heart entitled, “The Routine Use of Oxygen in the Treatment of Myocardial Infarction.”¹ This article stimulated me to opine on this topic, which has been an interest of mine for many years. Copyright © 2009 Wiley Periodicals, Inc.     

Authentication of food allergen quality by physicochemical and immunological methods

Purified allergens are required to detect cross‐contamination with other allergenic foods and to understand allergen interaction with other components of the food matrix. Pure allergens are also used for the diagnosis and treatment of food allergies. For example, serological methods are being developed to improve the quality of diagnosis, and to reduce the need for food challenge tests. In addition, recombinant allergens are being evaluated as candidate vaccines for safe and efficacious specific immunotherapy. Pure allergens are indispensable as reference materials for the calibration and standardization of methods between different laboratories and operators for risk assessment in the food industry. Therefore, there is a need for well‐defined purified food allergens. In this context, a panel of 46 food allergens from plant and animal sources has been purified, from either the food sources or as recombinant forms, within the EU‐funded EuroPrevall project. These allergens have been characterized by a battery of diagnostic tests demonstrating that they constitute an authentic, well‐defined library of comparable quality. The review summarizes the applications, potentials and limitations of key techniques used for the characterization and authentication of these allergen preparations, with a special emphasis on protein purity and identity, folding, post‐translational modifications and immunochemical properties. One key area identified is the development of powerful analytical techniques, such as mass spectrometry and nuclear magnetic resonance, to improve the authentication of allergens for routine applications in allergy management. Cite this as: A. I. Sancho, K. Hoffmann‐Sommergruber, S. Alessandri, A. Conti, M. G. Giuffrida, P. Shewry, B. M. Jensen, P. Skov and S. Vieths, Clinical & Experimental Allergy, 2010 (40) 973–986.     

Effects of the increase in neuronal fatty acids availability on food intake and satiety in mice

Rationale  

Neurons detect free fatty acids (FFAs) availability and use this nutritional status to modulate feeding and control body weight.