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Topic Review
Tryptase for Suspected Mast Cell Disorders
Tryptase has proven to be a very useful and specific marker to demonstrate mast cell activation and degranulation when an acute (i.e., within 4 h after the event) and baseline value (i.e., at least 24 h after the event) are compared and meet the consensus formula (i.e., an increase of 20% + 2). The upper limit of normal determined by the manufacturer is 11.4 ng/mL; however, this boundary has been the subject of debate. According to ECNM and AIM experts, the normal range of baseline tryptase should be 1 to 15 ng/mL. A genetic trait, hereditary alpha tryptasemia, characterized by an increased alpha coding TPSAB1 copy number is associated with a baseline value above 8 ng/mL. Elevated tryptase can also be found in chronic kidney disease, obesity, and hematological neoplasms. A tryptase > 20 ng/mL serves as a minor criterion to diagnose systemic mastocytosis and an increase in tryptase > 20% + 2 during an acute event is a required criterion in the diagnosis of mast cell activation syndrome. 
  • 726
  • 19 Dec 2023
Topic Review
Chitosan Nanoparticles in Preclinical Testing of Atherosclerosis
Chitosan is a linear polysaccharide composed of randomly distributed β-(1–4)-linked 2-amino-2-deoxy-d-glucopyranose (deacetylated units) and 2-acetamido-2-deoxy-d-glucopyranose (acetylated units). Chitosan is derived from chitin, a highly abundant natural biopolymer with a high cationic potential. Chitin is extracted from the exoskeleton of many living organisms, including crabs, shrimps, insects, and fungi.
  • 725
  • 15 Aug 2022
Topic Review
Immune Responses against SARS-CoV-2—Questions and Experiences
Understanding immune reactivity against SARS-CoV-2 is essential for coping with the COVID-19 pandemic. Herein, we discuss experiences and open questions about the complex immune responses to SARS-CoV-2. Some people react excellently without experiencing any clinical symptoms, they do not get sick, and they do not pass the virus on to anyone else (“sterilizing” immunity). Others produce antibodies, develop memory T cells, and do not get COVID-19 but transmit the virus to others (“protective” immunity). Some people get sick but recover. A varying percentage develops respiratory failure, systemic symptoms, clotting disorders, cytokine storms, or multi-organ failure; they subsequently decease. Some develop long COVID, a new, controversioal pathologic entity similar to fatigue syndrome or autoimmunity. In reality, COVID-19 is considered more of a systemic immune–vascular disease than a pulmonic disease, involving many tissues and the central nervous system. To fully comprehend the complex clinical manifestations, a profound understanding of the immune responses to SARS-CoV-2 is a good way to improve clinical management of COVID-19. Although neutralizing antibodies are an established approach to recognize an immune status, cellular immunity plays at least an equivalent or an even more important role. However, reliable methods to estimate the SARS-CoV-2-specific T cell capacity are not available for clinical routines. This deficit is important because an unknown percentage of people may exist with good memory T cell responsibility but a low number of or completely lacking peripheral antibodies against SARS-CoV-2. Apart from natural immune responses, vaccination against SARS-CoV-2 turned out to be very effective and much safer than naturally acquired immunity. Nevertheless, besides unwanted side effects of the currently available vector and mRNA preparations, concerns remain whether these vaccines will be strong enough to defeat the pandemic. Altogether, discussing important questions, and try to give answers based on the current knowledge and preliminary data from our laboratories. 
  • 718
  • 30 Nov 2021
Topic Review
Pathogenesis of Penile Squamous Cell Carcinoma
Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The development of targeted treatment is hindered by poor knowledge of the molecular landscape of PSCC. 
  • 712
  • 10 Mar 2022
Topic Review
Tachyarrhythmias in Congenital Heart Diseases
Major advances in pediatric cardiology in recent decades, especially surgical techniques, have resulted in an increasing number of patients with congenital heart disease (CHD) surviving to adulthood. This has generated new challenges, particularly with regards to the late onset of complex arrhythmias. Abnormal anatomy, surgical scarring, chronic hypoxemia, hemodynamic compromise, neuro-hormonal abnormalities, and genetic factors can all contribute to creating a unique substrate for arrhythmia development.
  • 710
  • 09 Feb 2022
Topic Review
Protein Kinase C Inhibitors for Cancer Therapy
The protein kinase C (PKC) family belongs to serine-threonine kinases and consists of several subtypes. Increasing evidence suggests that PKCs are critical players in carcinogenesis. Interest-ingly, PKCs exert both promotive and suppressive effects on tumor cell growth and metastasis, which have attracted immense attention. PKCs play a potential role as a target for therapeutic intervention in cancer from basic research and clinical trials.
  • 707
  • 29 Mar 2022
Topic Review
Congenital Zika Syndrome
Zika virus (ZIKV) is a single-stranded ribonucleic acid (RNA) flavivirus transmitted by arthropod vectors, in particular, Aedes aegypti (or yellow fever mosquito, also responsible for the transmission of Dengue and Chikungunya) and Aedes albopictus (or Asian tiger mosquito, also responsible for the transmission of Chikungunya and West Nile virus). The virus replicates in the insect’s epithelial cells and, eventually, in the salivary glands. 
  • 702
  • 21 Mar 2022
Topic Review
Systemic Bevacizumab for Recurrent Respiratory Papillomatosis
Respiratory recurrent papillomatosis (RRP) is a fatal disease with no known cure. In severe RRP cases, systemic bevacizumab (SB) could be used as adjuvant therapy. SB may be a promissory treatment and control option for RRP. More research is needed to evaluate the efficiency and adverse effects in various populations.
  • 699
  • 09 Feb 2023
Topic Review
Redox Dysregulation in Aging and COPD
With a rapidly growing elderly human population, the incidence of age-related lung diseases such as chronic obstructive pulmonary disease (COPD) continues to rise. COPD is a chronic irreversible disease of the lungs characterized by airflow limitation due to destruction of the lung parenchyma (emphysema) and/or remodelling of the small airways, and is currently the third leading cause of death in the Westernized world. The greatest risk factor for COPD is smoking, but not all smokers develop COPD and the reasons for disease susceptibility in these individuals remains poorly understood. In COPD, the alveolar architecture has been destroyed resulting in emphysemaand subsequent dyspnea (shortness of breath).
  • 694
  • 25 Nov 2021
Topic Review
Allergic Reactions to Vaccine Constituents
Vaccination is an essential public health measure that helps to reduce the burden of infectious diseases in children. Although vaccines have an excellent safety record and the association of severe allergic reactions is rare, public concerns about vaccine safety can lead to incomplete vaccination coverage in children with or without allergies. Therefore, it is important to understand the mechanisms and implications of allergic reactions to vaccines and define strategies to manage them to provide the safest care for vaccine recipients. Unlike drugs, which are the primary cause of immediate allergic reactions, vaccine excipients (i.e., substances used to formulate a vaccine) are the main cause of specific IgE and immediate reactions associated with vaccines. Pre-existing allergies to vaccine excipients, such as antigens, adjuvants, stabilizers, preservatives, emulsifiers, leached packaging components, residual antibiotics, cell culture materials, and inactivating ingredients, are the primary contributors to immediate allergic reactions during vaccination. In contrast, drug-related anaphylaxis is usually caused by the active drug itself rather than excipients.
  • 692
  • 21 Apr 2023
Topic Review
Foetal Nutrition and Allergic Disease
Complex interactions at the materno-placental-foetal interface have a profound influence on the infants’ immune maturation and the likelihood of developing allergic sensitisation and disease. Gene/environment interactions and timing of exposures through pregnancy add further degrees of complexity. Understanding the early life origins of allergy will only be possible by embracing this complexity. Studies will now need to investigate combinations of dietary, pollutant, medication and microbial exposures during pregnancy in relation to genomics, epigenomics, metagenomics and metabolomics and their effect on infant/child outcomes. Controlled trials of a “healthy diet” during pregnancy are likely to yield better outcomes than focusing on single nutrients which hitherto have produced disappointing results. The manipulation of the neonates’ evolving microbiome is suggested as another focus for controlled prevention trials.
  • 691
  • 29 Apr 2022
Topic Review
Genetic Polymorphisms of Cathepsin A
Cathepsin A (CatA) is important as a drug-metabolizing enzyme responsible for the activation of prodrugs, such as the anti-human immunodeficiency virus drug Tenofovir Alafenamide (TAF). 
  • 690
  • 13 Jan 2022
Topic Review
Motor and Cognitive Functions with Home-Confinement COVID-19
Distancing and confinement at home during the Coronavirus Disease 2019 (COVID-19) outbreak has led to worsening of motor and cognitive functions, both for healthy adults and for patients with neurodegenerative diseases. The decrease in physical activity, the cessation of the intervention of the recovery and the social distance imposed by the lockdown, has had a negative impact on the physical and mental health, quality of life, daily activities, as well as on the behavioral attitudes of the diet.
  • 690
  • 28 Feb 2022
Topic Review
Epigenetic and Childhood Asthma Development
Asthma is a common respiratory disease that affects people of all ages, characterized by considerable heterogeneity in age, clinical presentation, genetics, epigenetics, environmental factors, treatment response, and prognostic outcomes. Asthma affects more than 330 million people worldwide, of which 33% are children under 14 years, and 27% are adults whose first symptoms occurred in childhood. However, the genetic and epigenetic mechanisms of childhood allergic diseases and asthma are still not fully understood.
  • 690
  • 29 Jun 2023
Topic Review
Multitarget Antioxidant NO-Donor Organic Nitrates
Chronic use of glyceryl trinitrate (GTN) is limited by serious side effects, such as tolerance and endothelial dysfunction of coronary and resistance arteries. Although GTN is used as a drug since more than 130 years, the mechanisms of the vasodilatory effects and of tolerance development to organic nitrates are still incompletely elucidated. New synthesized organic nitrates with and without antioxidant properties were characterized for their ex vivo tolerance profile, in order to investigate the oxidative stress hypothesis of nitrate tolerance. The organic nitrates studied showed different vasodilation and tolerance profiles, probably due to the ability or inability of the compounds to interact with the aldehyde dehydrogenase-2 enzyme (ALDH-2) involved in bioactivation. Furthermore, nitrooxy derivatives endowed with antioxidant properties did not determine the onset of tolerance, even if bioactivated by ALDH-2. The results could be further evidence of the involvement of ALDH-2 in the development of nitrate tolerance. Moreover, the behavior of organic nitrates with antioxidant properties supports the hypothesis of the involvement of ROS in inactivating ALDH-2.
  • 689
  • 04 Mar 2022
Topic Review
Precision Allergy Molecular Diagnosis in Predicting Atopy Development
The allergic march is a progression of naturally occurring symptoms whose nature changes with age. The classic allergic march typically begins in infancy and manifests in the form of atopic dermatitis and food allergy. As immune tolerance develops over time, these conditions may resolve by the age of 3–5 years; however, they may evolve into allergic rhinitis and bronchial asthma. Traditional diagnostic assessments, such as skin prick testing or serum allergen-specific immunoglobulin E (sIgE) level testing, are conducted to introduce effective treatment. The precision allergy molecular diagnosis (PAMD@) assesses sIgE against allergenic molecules. This new technology helps more accurately evaluate the patient’s allergy profile, which helps create more precise dietary specifications and personalize allergen-specific immunotherapy.
  • 689
  • 31 Aug 2023
Topic Review
Vitamin D Status and Allergy Outcomes
The very early onset of allergic diseases points to the specific vulnerability of the developing immune system to environmental changes and the development of primary intervention strategies is crucial to address this unparalleled burden. Vitamin D is known to have immunomodulatory functions. While allergic disease is multifactorial, associations with reduced sunlight exposure have led to the hypothesis that suboptimal vitamin D levels during critical early periods may be one possible explanation. Interventions to improve vitamin D status, especially in early life, may be the key to allergic disease prevention.
  • 688
  • 28 Apr 2022
Topic Review
Effects of Therapeutic Antibodies on Transcriptome/Proteome of Asthma
Different gene clusters have been identified to change upon omalizumab treatment, found a reduction in eosinophil-associated gene signatures after benralizumab treatment, and protein profiles were different in patients treated with mepolizumab and in those treated with benralizumab. The main potential biomarkers proposed by the selected studies are shown. These results may contribute to discovering biomarkers of response and selecting the best therapy for each patient.
  • 686
  • 03 Mar 2022
Topic Review
Multidrug-Resistant Tuberculosis Treatment
Multidrug-resistant (MDR) tuberculosis (TB), resistant to isoniazid and rifampicin, continues to be one of the most important threats to controlling the TB epidemic. There have been promising pharmacological advances in the paradigm of MDR TB treatment: new and repurposed drugs have shown excellent bactericidal and sterilizing activity against Mycobacterium tuberculosis and several all-oral short regimens to treat MDR TB have shown promising results. 
  • 685
  • 25 Feb 2022
Topic Review
Infection in Chronic Obstructive Pulmonary Disease
The term chronic obstructive pulmonary disease (COPD) may not be precise in distinguishing various pulmonary conditions, including asthma, which can pose difficulties in distinguishing asthma from COPD, particularly among smokers and older adults. Moreover, some patients may exhibit clinical features that are common to both asthma and COPD. The diagnosis of pneumonia based solely on clinical signs and laboratory data can be challenging, given the variability of clinical presentations, particularly in the presence of chronic respiratory illness. The literature on COPD often lacks clarity in defining, documenting, classifying, and attributing pneumonia events in terms of severity. Furthermore, variations in the methods used to document and evaluate pneumonia across different countries can contribute to the variability in reported incidence rates, making cross-trial comparisons problematic. Patients with severe forms of COPD may experience exacerbations that can be challenging to differentiate clinically and radiographically from pneumonia, resulting in an overestimation of the number of pneumonia cases in these trials.
  • 681
  • 09 May 2023
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