The current role of sublingual immunotherapy in the treatment of allergic rhinitis in adults and children

Allergic rhinitis is a very common disease affecting about 20% of people. It may be treated by allergen avoidance when possible, by antiallergic drugs such as antihistamines and topical corticosteroids, and by allergen-specific immunotherapy. The latter is the only treatment able to act on the causes and not only on the symptoms of respiratory allergy and is able to maintain its efficacy even after stopping, provided an adequate duration of treatment of 3–5 years is ensured. Sublingual immunotherapy (SLIT) was introduced in the 1990s as a possible solution to the problem of adverse systemic reactions to subcutaneous immunotherapy and has been demonstrated by more than 50 trials and globally evaluated thus far by five meta-analyses as an effective and safe treatment for allergic rhinitis. Life-threatening reactions are extremely rare. However, it is important to note that clinical efficacy occurs only if SLIT meets its needs, ie, sufficiently high doses are regularly administered for at least 3 consecutive years. This is often overlooked in the current practice and may prevent the same success reported by trials from being achieved

The light and shadow of senescence and inflammation in cardiovascular pathology and regenerative medicine

Recent epidemiologic studies evidence a dramatic increase of cardiovascular diseases, especially associated with the aging of the world population. During aging, the progressive impairment of the cardiovascular functions results from the compromised tissue abilities to protect the heart against stress. At the molecular level, in fact, a gradual weakening of the cellular processes regulating cardiovascular homeostasis occurs in aging cells. Atherosclerosis and heart failure are particularly correlated with aging-related cardiovascular senescence, that is, the inability of cells to progress in the mitotic program until completion of cytokinesis. In this review, we explore the intrinsic and extrinsic causes of cellular senescence and their role in the onset of these cardiovascular pathologies. Additionally, we dissect the effects of aging on the cardiac endogenous and exogenous reservoirs of stem cells. Finally, we offer an overview on the strategies of regenerative medicine that have been advanced in the quest for heart rejuvenation

Molecular epidemiology and genotyping of Chlamydia trachomatis infection in a cohort of young asymptomatic sexually active women (18-25 years) in Milan, Italy.

IntroductionChlamydia trachomatis (Ct) is the most common bacterial cause of sexually transmitted infections (STI) and is associated with severe long-term sequelae in female populations.In Italy Ct infections are not submitted to a screening programme, and its epidemiological profile is understudied. Even scarcer information is available about the genetic diversity on ompA gene, whose sequence defines 18 different genovars.This study aims at evaluating the prevalence of Ct infection in young sexually active asymptomatic women aged 18-25, and characterizing the molecular epidemiology of the different circulating genovars in this population. MethodsCervical samples collected from 909 sexually-active-young women (mean age 21.5 years) were analyzed through molecular assay for the detection of Ct infection. Phylogenetic analysis on the ompA gene was performed on Ct positive samples to identify the circulating genovars. ResultsThe overall prevalence of Ct-infection was 4.4% (95%CI: 3.2-5.9%): 5.3% among women aged 18-21 years and 3.5% among those aged 22-25 years. Phylogenetic analysis has identified 5 different genovars: D, E, F, G, and H. The most common genovar was the E (46%), followed by genovar F and G (18.9% each), D (13.5%), and H (2.7%). ConclusionsThis study underlines the high prevalence of asymptomatic Ct-infections among young women. Overall, about half of asymptomatic infections is sustained by genovar E. The introduction in Italy of a systematic screening program should be considered to allow a better understanding of Ct spreading and providing women with an opportunity for early treatment to protect their sexual and reproductive health

Selection of reference genes for quantitative RT-PCR studies in striped dolphin (Stenella coeruleoalba) skin biopsies

BACKGROUND: Odontocete cetaceans occupy the top position of the marine food-web and are particularly sensitive to the bioaccumulation of lipophilic contaminants. The effects of environmental pollution on these species are highly debated and various ecotoxicological studies have addressed the impact of xenobiotic compounds on marine mammals, raising conservational concerns. Despite its sensitivity, quantitative real-time PCR (qRT-PCR) has never been used to quantify gene induction caused by exposure of cetaceans to contaminants. A limitation for the application of qRT-PCR is the need for appropriate reference genes which allow the correct quantification of gene expression. A systematic evaluation of potential reference genes in cetacean skin biopsies is presented, in order to validate future qRT-PCR studies aiming at using the expression of selected genes as non-lethal biomarkers. RESULTS: Ten commonly used housekeeping genes (HKGs) were partially sequenced in the striped dolphin (Stenella coeruleoalba) and, for each gene, PCR primer pairs were specifically designed and tested in qRT-PCR assays. The expression of these potential control genes was examined in 30 striped dolphin skin biopsy samples, obtained from specimens sampled in the north-western Mediterranean Sea. The stability of selected control genes was determined using three different specific VBA applets (geNorm, NormFinder and BestKeeper) which produce highly comparable results. Glyceraldehyde-3P-dehydrogenase (GAPDH) and tyrosine 3-monooxygenase (YWHAZ) always rank as the two most stably expressed HKGs according to the analysis with geNorm and Normfinder, and are defined as optimal control genes by BestKepeer. Ribosomal protein L4 (RPL4) and S18 (RPS18) also exhibit a remarkable stability of their expression levels. On the other hand, transferrin receptor (TFRC), phosphoglycerate kinase 1 (PGK1), hypoxanthine ribosyltransferase (HPRT1) and β-2-microglobin (B2M) show variable expression among the studied samples and appear as less suitable reference genes for data normalization. CONCLUSION: In this work, we have provided essential background information for the selection of control genes in qRT-PCR studies of cetacean skin biopsies, as a molecular technique to investigate ecotoxicological hazard in marine mammals. Of 10 HKGs tested, those encoding for YWHAZ and GAPDH appear as the most reliable control genes for the normalization of qRT-PCR data in the analysis of striped dolphin skin biopsies. Potentially useful reference genes are also those encoding for ribosomal proteins L4 and S18

Bone marrow-derived cells can acquire cardiac stem cells properties in damaged heart

Experimental data suggest that cell-based therapies may be useful for cardiac regeneration following ischaemic heart disease. Bone marrow (BM) cells have been reported to contribute to tissue repair after myocardial infarction (MI) by a variety of humoural and cellular mechanisms. However, there is no direct evidence, so far, that BM cells can generate cardiac stem cells (CSCs). To investigate whether BM cells contribute to repopulate the Kit+ CSCs pool, we transplanted BM cells from transgenic mice, expressing green fluorescent protein under the control of Kit regulatory elements, into wild-type irradiated recipients. Following haematological reconstitution and MI, CSCs were cultured from cardiac explants to generate 'cardiospheres', a microtissue normally originating in vitro from CSCs. These were all green fluorescent (i.e. BM derived) and contained cells capable of initiating differentiation into cells expressing the cardiac marker Nkx2.5. These findings indicate that, at least in conditions of local acute cardiac damage, BM cells can home into the heart and give rise to cells that share properties of resident Kit+ CSCs

A review of the molecular mechanisms underlying the development and progression of cardiac remodeling

Pathological molecular mechanisms involved in myocardial remodeling contribute to alter the existing structure of the heart, leading to cardiac dysfunction. Among the complex signaling network that characterizes myocardial remodeling, the distinct processes are myocyte loss, cardiac hypertrophy, alteration of extracellular matrix homeostasis, fibrosis, defective autophagy, metabolic abnormalities, and mitochondrial dysfunction. Several pathophysiological stimuli, such as pressure and volume overload, trigger the remodeling cascade, a process that initially confers protection to the heart as a compensatory mechanism. Yet chronic inflammation after myocardial infarction also leads to cardiac remodeling that, when prolonged, leads to heart failure progression. Here we review the molecular pathways involved in cardiac remodeling, with particular emphasis on those associated with myocardial infarction. A better understanding of cell signaling involved in cardiac remodeling may support the development of new therapeutic strategies towards the treatment of heart failure and reduction of cardiac complications. We will also discuss data derived from gene therapy approaches for modulating key mediators of cardiac remodeling

Caprine αs1-Casein Polymorphism: Characterisation of A, B, E and F Variants by Means of Various Biochemical and Molecular Techniques

Considering a wide interest for the characterisation of caprine αs1-casein variants and a large number of differently equipped laboratories, the objective of this study was to analyse and compare characteristics of caprine αs1-casein variants by means of various biochemical and molecular techniques. The most frequent caprine αs1-casein variants (A, B, E and F) were characterized by employing electrophoretic protein separation analyses (capillary electrophoresis, isoelectric focusing, and sodium dodecylsulfate polyacrylamide gel electrophoresis), chromatographic analysis (reversed phase-high performance liquid chromatography) as well as DNA analyses (ASA and real-time polymerase chain reaction approach). Further, we stressed weak and strong points for each method applied and provided information for the optimal and complementary use of those methods with respect to time, resolution and costs

Caprine αs1-Casein Polymorphism: Characterisation of A, B, E and F Variants by Means of Various Biochemical and Molecular Techniques

Considering a wide interest for the characterisation of caprine αs1-casein variants and a large number of differently equipped laboratories, the objective of this study was to analyse and compare characteristics of caprine αs1-casein variants by means of various biochemical and molecular techniques. The most frequent caprine αs1-casein variants (A, B, E and F) were characterized by employing electrophoretic protein separation analyses (capillary electrophoresis, isoelectric focusing, and sodium dodecylsulfate polyacrylamide gel electrophoresis), chromatographic analysis (reversed phase-high performance liquid chromatography) as well as DNA analyses (ASA and real-time polymerase chain reaction approach). Further, we stressed weak and strong points for each method applied and provided information for the optimal and complementary use of those methods with respect to time, resolution and costs