Acute interstitial nephritis with acetaminophen and alcohol intoxication

Drug-induced acute interstitial nephritis (AIN) represents a growing cause of renal failure in current medical practice. While antimicrobials and non-steroidal anti-inflammatory drugs are typically associated with drug-induced AIN, few reports have been made on the involvement of other analgesics. We report our experience in managing a 17-year-old female with AIN and subsequent renal injury following an acetaminophen overdose in conjunction with acute alcohol intoxication. It is well established that acetaminophen metabolism, particularly at high doses, produces reactive metabolites that may induce renal and hepatic toxicity. It is also plausible however, that such reactive species could instead alter renal peptide immunogenicity, thereby inducing AIN. In the following report, we review a possible mechanism for the acetaminophen-induced AIN observed in our patient and also discuss the potential involvement of acute alcohol ingestion in disease onset. The objective of our report is to increase awareness of healthcare professionals to the potential involvement of these commonly used agents in AIN pathogenesis

CT Diagnosis of an Abortion-Related Retroperitoneal Space Abscess

A female patient with a history of recent abortion was transferred in critically ill condition in our hospital. CT imaging on emergency basis depicted an abscess in the right retroperitoneal space that included the head of fetus, along with rupture of the right lateral wall of uterus. Spiral CT enabled prompt diagnosis and therapy of this rare abortion-related complication

Immune and inflammatory responses in TNF alpha-deficient mice: A critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response

To investigate the role of TNF alpha in the development of in vivo immune response we have generated TNF alpha-deficient mice by gene targeting. Homozygous mutant mice are viable and fertile, develop lymph nodes and Peyer's patches and show no apparent phenotypic abnormalities, indicating that TNF alpha is not required for normal mouse development. In the absence of TNF alpha mice readily succumb to L. monocytogenes infections and show reduced contact hypersensitivity responses. Furthermore, TNF alpha knockout mice are resistant to the systemic toxicity of LPS upon D-galactosamine sensitization, yet they remain sensitive to high doses of LPS alone. Most interestingly, TNF alpha knockout mice completely lack splenic primary B cell follicles and cannot form organized follicular dendritic cell (FDC) networks and germinal centers. However, despite the absence of B cell follicles, Ig class-switching can still occur, yet deregulated humoral immune responses against either thymus-dependent (TD) or thymus-independent (TI) antigens are observed. Complementation of TNF alpha functioning by the expression of either human or murine TNF alpha transgenes is sufficient to reconstitute these defects, establishing a physiological role for TNF alpha in regulating the development and organization of splenic follicular architecture and in the maturation of the humoral immune response

Future yields assessment of bioenergy crops in relation to climate change and technological development in Europe

Bioenergy crops are expected to play an important role in reducing CO2 emission, in energy supply and in European energy policy. However, a sustainable bioenergy supply must be resilient to climate change and the impacts on agriculture at both global and regional scale. The purpose of this study was to forecast the potential distribution of several bioenergy crops based on agronomic and environmental constrains under current conditions and future scenarios (2020 and 2030) in European Union. Potential biomass yield, according to the category end use product achievable in each environmental zone of Europe at present and in the future available land have been also studied. Future yields were assessed according to two factors: technological development and climate change: the former was based on prospect of DG-Agriculture for conventional crops and expert judgments for bioenergy crops, while the latter based on relevant research papers and literature reviews which used site-specific crop growth models. Yields are expected to increase in northern Europe due to climate change and technological development, while in southerneastern Europe the negative effect of climate change will be mitigated by the technological development. The estimated total biomass production in Europe, on the basis of future yields and surplus land made available for energy crops, may not be sufficient to meet the needs of bioenergy supply as claimed in the European directive 2009/28/EC

Innate immunity: ignored for decades, but not forgotten.

The innate immune system must recognize and rapidly respond to microbial pathogens, providing a first line of host defense. This is accomplished through an array of pattern recognition receptors (PRRs) that reside in specific subcellular compartments and can bind pathogen-associated molecular patterns. PRRs also recognize self-molecules that are released after cell damage or death, known as danger-associated molecular patterns, which can be actively transported across cell membranes. The activation of PRRs leads to host defense pathways in infectious diseases, but can also contribute to tissue injury in autoimmune diseases. The identification of these pathways has provided new insight into mechanisms of vaccination and holds promise for developing better vaccines. Finally, the identification of PRRs, their ligands, and signaling pathways provides an opportunity for developing new immunotherapeutic approaches to skin conditions in which activation of the innate immune response contributes to disease pathogenesis

The effects of integrated food and bioenergy cropping systems on crop yields, soil health, and biomass quality: The EU and Brazilian experience

Integrated food and bioenergy production is a promising way to ensure regional/national food and energy security, efficient use of soil resources, and enhanced biodiversity, while contributing to the abatement of CO2 emissions. The objective of this study was to assess alternative crop rotation schemes as the basis for integrating and enhancing the sustainable biomass production within the food-energy agricultural context. Sunn hemp (Crotalaria spp.) in rotation with wheat (Triticum spp.) in the EU and with sugarcane (Saccharum spp.) in Brazil were evaluated. Sunn hemp did not negatively affect crop's productivity and soil fertility; wheat grain yields were maintained around the mean regional production levels (6, 7, 3 and Mg ha(-1) in Greece, Italy, and Spain, respectively), and the cumulative biomass in the extended rotation (wheat straw+sunn hemp) was between 1.5 and 2.0 times higher than in the conventional rotation. In Brazil, sugarcane stalks yield in clay soils increased by around 15 Mg ha(-1) year(-1) under sunn hemp rotation in comparison with bare fallow. Moreover, sunn hemp in the EU rotations did not have negative effects on soil available macronutrients, organic matter, pH, and cation exchange capacity, neither on C and N stocks in Brazil. The qualitative characteristics (mineral, ash, and hemicelluloses contents) of the cumulated biomass were somehow higher (in average +26%, +35%, and +3.4%, respectively) than in the conventional system. In summary, in temperate and tropical climates the integration of dedicated biomass legume crops within conventional systems could lead to enhanced biomass availability, crop diversification, and efficient use (in space and time) of the land resources

Cover to Volume 3

The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth

Paediatric radiation therapy across Europe: A European questionnaire survey supported by the SIOPe, ESTRO, PROS and several national paediatric hematology-oncology societies (NAPHOS)

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Using distinct molecular signatures of human monocytes and dendritic cells to predict adjuvant activity and pyrogenicity of TLR agonists

We present a systematic study that defines molecular profiles of adjuvanticity and pyrogenicity induced by agonists of human Toll-like receptor molecules in vitro. Using P3CSK4, Lipid A and Poly I:C as model adjuvants we show that all three molecules enhance the expansion of IFNγ+/CD4+ T cells from their naïve precursors following priming with allogeneic DC in vitro. In contrast, co-culture of naive CD4+ T cells with allogeneic monocytes and TLR2/TLR4 agonists only resulted in enhanced T cell proliferation. Distinct APC molecular signatures in response to each TLR agonist underline the dual effect observed on T cell responses. Using protein and gene expression assays, we show that TNF-α and CXCL10 represent DC-restricted molecular signatures of TLR2/TLR4 and TLR3 activation, respectively, in sharp contrast to IL-6 produced by monocytes upon stimulation with P3CSK4 and Lipid A. Furthermore, although all TLR agonists are able to up-regulate proIL-1β specific gene in both cell types, only monocyte activation with Lipid A results in detectable IL-1β release. These molecular profiles, provide a simple screen to select new immune enhancers of human Th1 responses suitable for clinical application