Sublingual immunotherapy: administration, dosages, use

Allergen extracts for sublingual immunotherapy (SLIT) are currently marketed by several manufacturers, with administration schedules and amount of allergen(s) quite variable in the different products, although almost all are standardized biologically or immunologically. The allergen extracts for SLIT are available in two main pharmaceutical forms: solution to be delivered by drop-counters, pre-dosed actuators (mini-pumps) or disposable single-dose vials; tablets with appropriate composition that allows a slow (1-2 minutes) dissolution in the mouth in contact with saliva. In Europe, SLIT is prescribed in general for one or a few allergens, and mixtures are less used, though there is no immunological contraindication to give multiple allergens. SLIT traditionally involves a build-up phase and a maintenance phase with the top dose. The build-up phase has usually the duration of 4 - 6 weeks. The patient must start with the lowest concentration and gradually increase, using the different dosage preparations, until the maintenance dose is reached. Rush and ultra-rush inductions have been introduced, based on the safety profile of SLIT that is very favorable. For these reasons it has been suggested that an updosing phase maybe even not necessary. The no-updosing approach would result in a treatment that is more patient-friendly and convenient to manage. Indeed, the most recent randomized trials were performed with the no-updosing regimen and their results in term of safety were as favorable as the studies performed with the traditional updosing approach. The currently recommended duration of SLIT is comprised between 3 and 4 years depending on the clinical response in single patients

Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene

BACKGROUND: There are three pathways of L-threonine catabolism. The enzyme L-threonine aldolase (TA) has been shown to catalyse the conversion of L-threonine to yield glycine and acetaldehyde in bacteria, fungi and plants. Low levels of TA enzymatic activity have been found in vertebrates. It has been suggested that any detectable activity is due to serine hydroxymethyltransferase and that mammals lack a genuine threonine aldolase. RESULTS: The 7-exon murine L-threonine aldolase gene (GLY1) is located on chromosome 11, spanning 5.6 kb. The cDNA encodes a 400-residue protein. The protein has 81% similarity with the bacterium Thermotoga maritima TA. Almost all known functional residues are conserved between the two proteins including Lys242 that forms a Schiff-base with the cofactor, pyridoxal-5'-phosphate. The human TA gene is located at 17q25. It contains two single nucleotide deletions, in exons 4 and 7, which cause frame-shifts and a premature in-frame stop codon towards the carboxy-terminal. Expression of human TA mRNA was undetectable by RT-PCR. In mice, TA mRNA was found at low levels in a range of adult tissues, being highest in prostate, heart and liver. In contrast, serine/threonine dehydratase, another enzyme that catabolises L-threonine, is expressed very highly only in the liver. Serine dehydratase-like 1, also was most abundant in the liver. In whole mouse embryos TA mRNA expression was low prior to E-15 increasing more than four-fold by E-17. CONCLUSION: Mice, the western-clawed frog and the zebrafish have transcribed threonine aldolase/GLY1 genes, but the human homolog is a non-transcribed pseudogene. Serine dehydratase-like 1 is a putative L-threonine catabolising enzyme

Adherence issues related to sublingual immunotherapy as perceived by allergists

Objectives: Sublingual immunotherapy (SLIT) is a viable alternative to subcutaneous immunotherapy to treat allergic rhinitis and asthma, and is widely used in clinical practice in many European countries. The clinical efficacy of SLIT has been established in a number of clinical trials and meta-analyses. However, because SLIT is self-administered by patients without medical supervision, the degree of patient adherence with treatment is still a concern. The objective of this study was to evaluate the perception by allergists of issues related to SLIT adherence. Methods: We performed a questionnaire-based survey of 296 Italian allergists, based on the adherence issues known from previous studies. The perception of importance of each item was assessed by a VAS scale ranging from 0 to 10. Results: Patient perception of clinical efficacy was considered the most important factor (ranked 1 by 54% of allergists), followed by the possibility of reimbursement (ranked 1 by 34%), and by the absence of side effects (ranked 1 by 21%). Patient education, regular follow-up, and ease of use of SLIT were ranked first by less than 20% of allergists. Conclusion: These findings indicate that clinical efficacy, cost, and side effects are perceived as the major issues influencing patient adherence to SLIT, and that further improvement of adherence is likely to be achieved by improving the patient information provided by prescribers. © 2010 Scurati et al, publisher and licensee Dove Medical Press Ltd

Indacaterol in the Treatment of Chronic Obstructive Pulmonary Disease: From Clinical Trials to Daily Practice

Indacaterol was introduced as an agent of the new generation of very long acting beta2-agonists (VLABA) that provides a 24-hour activity of bronchodilation and allows a once-daily OD dosing. The first trial showed a significantly higher efficacy of indacaterol vs. placebo in patients with chronic obstructive pulmonary disease (COPD). The following trials were aimed at evaluating its performance compared with other bronchodilators. The results can be summarized in a comparable efficacy of indacaterol, mainly assessed by the increase in FEV1 value but also by quality of life and other patient- reported outcomes (PROs), compared with the OD antimuscarinic tiotropium bromide, and in a slightly higher efficacy compared with the LABA formoterol and salmeterol administered twice-daily. No problems of safety and tolerability were reported in the trials as well as in specific studies, every kind of adverse event, including cardiovascular effects, being similarly frequent with indacaterol and with placebo. Concerning the real-life management, in respect to LABA, the OD dosing makes indacaterol more convenient for COPD patients and is likely to positively influence the patient's adherence. Since adherence to medical treatment of chronic diseases, and particularly COPD is a crucial issue in medicine, such aspect should confer to indacaterol a valuable role in clinical practice. The recently approved combination of indacaterol with the antimuscarinic glycopyrronium [QVA149], based on the demonstration of positive effects on both lung function and PROs, is likely to be a further option for patients with severe COPD

Lipoprotein (a) plasma levels and lipoprotein status: comparison among adult healthy subjects, hospitalized patients and free living over 80 years old

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Lipoprotein (a) plasma levels and lipoprotein status: comparison among adult healthy subjects, hospitalized patients and free living over 80 years old

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Chronic Obstructive Pulmonary Disease

Different outcomes of pulmonary rehabilitation in patients with COPD with or without exacerbation