Mast cells in allergic and inflammatory diseases

Mast cells are important in the development of allergic and anaphylactic reactions, but also in acquired and innate immunity. There is also increasing evidence that mast cells participate in inflammatory diseases, where they can be activated by non-allergic triggers, such as neuropeptides and cytokines, often having synergistic effects as in the case of substance P (SP) and IL-33. Secretion of vasoactive mediators, cytokines and proteinases contribute to the development of coronary artery disease (CAD), as well as to diet-induced obesity and the metabolic syndrome. Mast cells may be able to orchestrate such different biological processes through their ability to release pro-inflammatory mediators selectively without the degranulation typical of allergic reactions. Recent evidence suggests that mitochondrial uncoupling protein 2 (UCP2) and mitochondrial translocation regulate mast cell degranulation, but not selective mediator release. Better understanding of these two processes and how mast cells exert both immunostimulatory and immunosuppressive actions could lead to the development of inhibitors of release of specific mediators with novel therapeutic applications.     

Cell attachment and response to photocured, degradable bone adhesives containing tricalcium phosphate and purmorphamine

The aim of this study was to quantify and provide evidence as to how addition of tricalcium phosphate (β-TCP) and the Hedgehog agonist purmorphamine to a degradable bone adhesive affects cell attachment/proliferation and Hedgehog pathway activation. Fourier transform infrared spectroscopy demonstrated that high levels (75 wt.%) of β-TCP addition reduced the photocure rate of the chosen poly(propylene glycol-co-lactide) dimethacrylate (PPLM) bone adhesive, but this problem was overcome by increased light exposure. In phosphate-buffered saline the total surface mass loss of set 15 mm diameter PPLM films was ～3.2 mg in 12 weeks, irrespective of thickness (200 or 400 μm) or β-TCP level (50 or 75 wt.%). With 400 μm samples there was additional bulk material loss. Proliferation of pre-osteoblast cells (MC3T3-E1) on the set adhesive surfaces was enhanced by decreased sample thickness or filler content increase. Degradation evidence suggested that both effects were due to reduced acidic polymeric degradation products. Activation of the Hedgehog pathway was quantified by measuring Gli expression in Light II reporter cells. The 0.01 and 0.1 wt.% purmorphamine in composite discs (400 μm, 75 wt.% β-TCP) enhanced Gli expression of attached cells 2- and 5-fold, respectively, without influencing their number. Pre-storage of the composite samples in culture medium had no detrimental effect on this response. Furthermore, sample storage medium gave no enhanced Gli expression in cells on tissue culture plastic. This suggests drug release levels were very low. Purmorphamine and β-TCP incorporation in PPLM adhesives might, therefore, provide prolonged enhancement of in vivo bone repair without systemic drug side-effects.     

Characterization of Enterobius vermicularis in a human population, employing a molecular-based method from adhesive tape samples

Human infection with the parasitic nematode Enterobius vermicularis occurs worldwide, particularly in children. Although its prevalence may exceed 35% in some parts of the world, molecular studies of E. vermicularis in humans are limited. The aim of the present study was to investigate the genetic variation within E. vermicularis in a human population. For this purpose, 77 adhesive tape samples taken from Greek children infested with E. vermicularis were tested. New primers were designed to amplify a segment of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of E. vermicularis from adhesive tape samples. Thirty-six amplicons were sequenced and eleven different haplotypes were identified. All sequences clustered within the type previously characterized (type B), only reported to date from captive chimpanzees. To the best of our knowledge, this is the first study of E. vermicularis genotypes from a human population.     

Association of the idiotype:antiidiotype antibody ratio with the efficacy of intravenous immunoglobulin treatment for the prevention of recurrent autoimmune‐associated congenital heart block

Objective

Congenital heart block (CHB), a manifestation of neonatal lupus, is associated with maternal anti‐Ro/SSA and anti‐La/SSB autoantibodies and recurs in ∼18% of subsequent pregnancies. This study was undertaken to investigate the effect of the idiotype:antiidiotype (Id:anti‐Id) antibody ratio in the ability of intravenous immunoglobulin (IVIG) administered during subsequent pregnancies to prevent CHB.

Methods

We studied 16 anti‐Ro/SSA and anti‐La/SSB–positive pregnant women from the Preventive IVIG Therapy for Congenital Heart Block study who had previously given birth to a child with neonatal lupus. In 3 of the mothers, the study pregnancy resulted in the birth of a child with neonatal lupus (2 with CHB and 1 with rash). Sequential serum samples were obtained from all mothers immediately before the administration of IVIG during pregnancy and were evaluated for antibodies against the major B cell epitope 349–364aa of La/SSB (idiotype) and its antiidiotypic antibodies.

Results

Following IVIG treatment, serum titers of anti‐La(349–364) (Id antibodies) decreased in 80% of the mothers, and in 60% an increase in anti‐Id antibodies against anti‐La(349–364) was observed. The Id:anti‐Id ratio was significantly higher in mothers whose offspring developed neonatal lupus compared to mothers who gave birth to a healthy child (P < 0.0001). Removal of anti‐Id antibodies substantially increased the reactivity against La(349–364) in sera from 5 of 7 mothers tested. All IVIG preparations were examined for Id and anti‐Id antibody activity. IVIG from batches administered to mothers who gave birth to a healthy child had an Id:anti‐Id activity ratio of <1, in contrast to that given to mothers who gave birth to a child with neonatal lupus. Addition of the IVIG preparations to the maternal sera further enhanced antiidiotypic activity (by up to 4.7‐fold) in 11 of 13 patients studied.

Conclusion

This is the first study in humans to demonstrate that IVIG influences the Id–anti‐Id network of a specific pathogenic autoantibody. Specifically, we showed that IVIG enhanced the anti‐Id antibody response in pregnant women with anti‐La/SSB antibodies. A high Id:anti‐Id ratio in both the IVIG preparation and the maternal serum may explain the absence of an effect of IVIG in preventing recurrent neonatal lupus in some cases.

     

Rapid ventricular pacing: a fast, reliable, and safe technique for optimization of image acquisition during rotational angiography for catheter ablation of atrial fibrillation

Rotational angiography is a novel method for three-dimensional reconstruction of the left atrium and pulmonary veins during catheter ablation for atrial fibrillation, but is still hampered by suboptimal reconstructions in a considerable number of patients. We describe the results of rapid pacing of the right ventricle for optimization of image acquisition during rotational angiography.     

Additional funding mechanisms for Public Hospitals in Greece: the case of Chania Mental Health Hospital

Objectives  

To investigate whether the long term lease of public hospital owned land could be an additional financing mechanism for Greek public (mental) health hospitals.     

The impact of endovascular management on the outcome of aneurysmal subarachnoid hemorrhage in the elderly in Eastern Finland

Background

The International Subarachnoid Aneurysm Trial (ISAT) concluded that “there is currently no reason to doubt that the reduction of dependent survival or death after endovascular coiling seen in all patients in the ISAT cohort should not be valid in the elderly”. We feel that this generalization requires further investigation to assess its validity.

Methods

We studied the impact of treatment era and independent risk factors for outcome in 179 consecutive elderly (≥70 years) aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to Kuopio University Hospital either between 1983 and 1992 (Era I, n?=?56), prior to the introduction of endovascular management, or between 1995 and 2004 (Era II, n?=?123) when the endovascular treatment was established at our institute. Altogether 150 patients underwent occlusive aneurysm treatment, 47 clipping in the Era I as against 49 clipping, 49 endovascular therapy, and five combination therapy in the Era II.

Results

The 12-month survival (n?=?179) did not improve from the Era I to the Era II. The proportion of good outcome (GOS IV–V) after occlusive therapy (n?=?150) was equal in the Era I and Era II (n?=?27/47; 57% vs. n?=?56/103; 54%). In multivariate logistic regression analysis, independent predictors of poor outcome were age, poor grade (Hunt&Hess IV–V), hydrocephalus, hypertension, and intraventricular hemorrhage, but not the mode of occlusive therapy (microsurgical vs. endovascular)

Conclusion

Clinical severity of the SAH was the most significant predictor of outcome. Integration of coil treatment in clinical practice has not improved the overall outcome of aSAH in the elderly at our institute.