Nucleotide oligomerization domain 1 is a dominant pathway for NOS2 induction in vascular smooth muscle cells: comparison with Toll-like receptor 4 responses in macrophages

Background and purpose:

Gram-negative bacteria contain ligands for Toll-like receptor (TLR) 4 and nucleotide oligomerization domain (NOD) 1 receptors. Lipopolysaccharide (LPS) activates TLR4, while peptidoglycan products activate NOD1. Activation of NOD1 by the specific agonist FK565 results in a profound vascular dysfunction and experimental shock in vivo.

Experimental approach:

Here, we have analysed a number of pharmacological inhibitors to characterize the role of key signalling pathways in the induction of NOS2 following TLR4 or NOD1 activation.

Key results:

Vascular smooth muscle (VSM) cells expressed NOD1 mRNA and protein, and, after challenge with Escherichia coli or FK565, NOS2 protein and activity were induced. Macrophages had negligible levels of NOD1 and were unaffected by FK565, but responded to E. coli and LPS by releasing increased NO and expression of NOS2 protein. Classic pharmacological inhibitors for NF-κB (SC-514) and mitogen-activated protein kinase (SB203580, PD98059) signalling pathways inhibited responses in both cell types regardless of agonist. While TLR4-mediated responses in macrophages were specifically inhibited by the pan-caspase inhibitor z-VAD-fmk and the PKC inhibitor Gö6976, NOD1-mediated responses in VSM cells were inhibited by the Rip2 inhibitor PP2.

Conclusions and implications:

Our findings suggest a selective role for NOD1 in VSM cells, and highlight NOD1 as a potential novel therapeutic target for the treatment of vascular inflammation.     

Effectiveness and Safety of Percutaneous CT-Guided Rib Biopsy

Purpose

To retrospectively evaluate effectiveness and safety of percutaneous CT-guided rib biopsy.

Short-term effects of biocorrodible iron stents in porcine coronary arteries

BACKGROUND: Biocorrodible iron stents carry the potential to overcome limitations, such as chronic inflammation and premature recoil, posed by biodegradable polymer and magnesium alloy stents. This study aimed to test the safety and efficacy of biocorrodible iron stents in porcine coronary arteries. METHODS: Iron stents and cobalt chromium stents were randomly deployed in the coronary arteries of juvenile domestic pigs. Animals were sacrificed at 28 days, and the vessels were fixed and processed for histochemistry. RESULTS: At 28 days, iron stents started to show signs of degradation without evidence of stent particle embolization or thrombosis without traces of excess inflammation, or fibrin deposition. At 28 days, the surface of the iron stent struts was black to brown and the vascular wall adjacent to the iron stent had a brownish tinge. There were no statistically significant differences in any of the measured parameters between segments implanted with iron and cobalt chromium stents. There were also no adverse effects in the persistent areas. CONCLUSION: The current study demonstrates that stents made of biocorrodible iron are safe. In some of the measured parameters, such as intimal thickness, intimal area, and percentage occlusion, there was a trend in favor of the iron stents.     

Follow‐up after systemic adverse reactions of immunotherapy

Out of 280 immunotherapy (IT)-treated patients in our allergy clinic, 37 (13%) developed systemic adverse reactions. Parietaria judaica (Pj) extract, a highly allergenic pollen in northern Israel, was part of the IT regimen in 46% of treated patients who developed systemic adverse reactions. Twenty-six (70%) of systemic adverse reactions occurred during the buildup phase, whereas 11 (30%) occurred in the maintenance phase of treatment. Mild systemic reactions developed in 15/37 (40%), moderate in 20/37 (54%), and severe in 2/37 (5%) of patients. In 22/37 (59% of our IT-treated patients, adverse reactions developed within 30 min after injection. Among these were the two patients with severe systemic reactions. In 19%, moderate adverse reactions appeared at 30-60 min; in 22%, mild to moderate reactions appeared after 1-2 h. Our study concludes that severe systemic reactions to IT usually appear within 30 min after injection. In Israel, IT with highly allergenic pollens such as Pj frequently causes systemic reactions, even during the maintenance phase of treatment. In such cases, the reduction of IT dosage should be more than 50% during the pollen season, and a waiting period of 1 h should also be considered.     

Use and effectiveness of dapagliflozin in routine clinical practice: An Italian multicentre retrospective study

In randomized controlled trials (RCTs), sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors have been shown to confer glycaemic and extra‐glycaemic benefits. The DARWIN‐T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) study was a multicentre retrospective study designed to evaluate the baseline characteristics of patients receiving dapagliflozin vs those receiving selected comparators (dipeptidyl peptidase‐4 inhibitors, gliclazide, or glucagon‐like peptide‐1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281 217, the analysis included 17 285 patients initiating dapagliflozin or comparator glucose‐lowering medications (GLMs), 6751 of whom had a follow‐up examination. At baseline, participants starting dapagliflozin were younger, had a longer disease duration, higher glycated haemoglobin (HbA1c) concentration, and a more complex history of previous GLM use, but the clinical profile of patients receiving dapagliflozin changed during the study period. Dapagliflozin reduced HbA1c by 0.7%, body weight by 2.7 kg, and systolic blood pressure by 3.0 mm Hg. Effects of comparator GLMs were also within the expected range, based on RCTs. This real‐world study shows an initial channelling of dapagliflozin to difficult‐to‐treat patients. Nonetheless, dapagliflozin provided significant benefits with regard to glucose control, body weight and blood pressure that were in line with findings from RCTs.     

Autism and the African American community

It is estimated that autism spectrum disorders (ASD) affect 1 in 500 live births per year. However, due to varying techniques for diagnosis and treatment, the disability remains the subject of debate. African Americans tend to suffer disproportionate rates of disability and disease when compared to other racial and ethnic groups due to access to preventative and curative care. However, evidence demonstrates that although rates of diagnosis for autism occur at the same rates in all racial groups, diagnosis in African American children occurs later than in White children. As a result, African American children may require longer and more intensive intervention. This article examines the etiology of autism, diagnosis, and treatment strategies and its impact on African American families. A case method approach is utilized to describe the impact of autism on an African American family. Implications for future research and professional practice and policy are discussed. Understanding autism is important as it relates to the human genome.     

Internet-based surveillance of Influenza-like-illness in the UK during the 2009 H1N1 influenza pandemic

Background  

Internet-based surveillance systems to monitor influenza-like illness (ILI) have advantages over traditional (physician-based) reporting systems, as they can potentially monitor a wider range of cases (i.e. including those that do not seek care). However, the requirement for participants to have internet access and to actively participate calls into question the representativeness of the data. Such systems have been in place in a number of European countries over the last few years, and in July 2009 this was extended to the UK. Here we present results of this survey with the aim of assessing the reliability of the data, and to evaluate methods to correct for possible biases.     

Civil defence in a nuclear disaster

Any nuclear war would be horrific and our main aim should be universal abolition of nuclear weapons. Civil defence, with its medical attributes, could certainly increase the survival rate should a disaster occur. The effect of the explosion of a nuclear warhead is outlined, together with what could be done to reduce casualties. Nuclear winter is discussed and it is suggested that the results of computerization of doubtful surmises have been treated too much as proven facts. The possibility of its occurrence should not deter emergency planning. Civil defence can save lives, and the fact that medicine as we know it would cease to exist in an all‐out nuclear war does not excuse us from doing what we can to increase the survival rate, if the worst should happen. Action should therefore be taken now to plan decentralization of resources and to instruct the public in protection, first aid and self‐sufficiency.