A Comparison of Molecular Techniques for Improving the Methodology in the Laboratory of Pharmacogenetics.

One of the most critical goals in healthcare is safe and effective drug therapy, which is directly related to an individual's response to treatment. Precision medicine can improve drug safety in many scenarios, including polypharmacy, and it requires the development of new genetic characterization methods. In this report, we use real-time PCR, microarray techniques, and mass spectrometry (MALDI-TOF), which allows us to compare them and identify the potential benefits of technological improvements, leading to better quality medical care.

Clinical and Genetic Characterization of a Cohort of Small-for-Gestational-Age Patients: Cost-Effectiveness of Whole-Exome Sequencing and Effectiveness of Treatment with GH.

Develop a clinical and genetic characterization, in a group of small-for-gestational-age (SGA) patients who did not experience catch-up growth In an ambispective cohort study with (SGA) patients. These patients received one treatment with growth hormone (GH) over 14 years. This study analyzes their response to treatment and conducts a genetic analysis in order to identify cases with specific phenotypic and auxological characteristics, defined as presenting two or more dysmorphic traits and/or a stature below -3 SDS (standard deviation score).

PTEN hamartoma tumor syndrome: Clinical and genetic characterization in pediatric patients.

Objective: The aim of this study was to provide a full characterization of a cohort of 11 pediatric patients diagnosed with PTEN hamartoma tumor syndrome (PHTS).

Patients And Methods: Eleven patients with genetic diagnostic of PHTS were recruited between February 2019 and April 2023. Clinical, imaging, demographic, and genetic data were retrospectively collected from their hospital medical history.

Case Report: Pharmacogenetics Applied to Precision Psychiatry Could Explain the Outcome of a Patient With a New Genotype.

Precision medicine applied to psychiatry provides new insight into the promising field of precision psychiatry. Psychotic disorders are heterogeneous, complex, chronic, and severe mental disorders. Not only does the prognosis and the course of the disease vary among patients suffering from psychotic disorders, but the treatment response varies as well.

Ten Years of Experience Support Pharmacogenetic Testing to Guide Individualized Drug Therapy.

Precision medicine utilizing the genetic information of genes involved in the metabolism and disposition of drugs can not only improve drug efficacy but also prevent or minimize adverse events. Polypharmacy is common among multimorbid patients and is associated with increased adverse events. One of the main objectives in health care is safe and efficacious drug therapy, which is directly correlated to the individual response to treatment.

Economic Impact of the Application of a Precision Medicine Model (5SPM) on Psychotic Patients.

Background: Schizophrenia is a severe mental disorder that often manifests within the first three decades of life. Its prognosis is uncertain and may result in a prolonged treatment that could extend throughout the entire lifespan of the patient. Antipsychotic drugs are characterized by a high interindividual variability when considering therapeutic effect and emergence of adverse effects.

Increased Copy Number in a Family With Elevated Basal Serum Levels of Tryptase.

Some recent familial studies have described a pattern of autosomal dominant inheritance for increased basal serum tryptase (BST), but no correlation with mRNA expression and gene dose have been reported. We analyzed mRNA expression and gene dose in a four-member family with high BST and in two control subjects. Blood samples were collected from the family and control subjects.

Application of a Pharmacogenetics-Based Precision Medicine Model (5SPM) to Psychotic Patients That Presented Poor Response to Neuroleptic Therapy.

Antipsychotics are the keystone of the treatment of severe and prolonged mental disorders. However, there are many risks associated with these drugs and not all patients undergo full therapeutic profit from them. The application of the 5 Step Precision Medicine model(5SPM), based on the analysis of the pharmacogenetic profile of each patient, could be a helpful tool to solve many of the problematics traditionally associated with the neuroleptic treatment.

A rare HCN4 variant with combined sinus bradycardia, left atrial dilatation, and hypertrabeculation/left ventricular noncompaction phenotype.

Introduction And Objectives: HCN4 variants have been reported to cause combined sick sinus syndrome (SSS) and left ventricular noncompaction (LVNC) cardiomyopathy. This relationship has been proven in few cases and no previous patients have associated left atrial dilatation (LAD). Our objective was to study a familial disorder characterized by SSS, LAD, and hypertrabeculation/LVNC and to identify the underlying genetic and electrophysiological characteristics.

YRNAs overexpression and potential implications in allergy.

Background: Small non-coding RNAs (snRNAs) develop important functions related to epigenetic regulation. YRNAs are snRNAs involved in the initiation of DNA replication and RNA stability that regulate gene expression. They have been related to autoimmune, cancer and inflammatory diseases but never before to allergy.

PTGDR expression is upregulated through retinoic acid receptors (RAR) mechanism in allergy.

Functional studies suggest that promoter polymorphisms of the Prostaglandin D Receptor (PTGDR) gene can be involved in asthma. All-trans Retinoic acid (ATRA) has also been linked to allergic diseases. We have previously described the PTGDR promoter activation mediated by ATRA through response elements (RARE) at position -549T> C.

Cluster Analysis Identifies 3 Phenotypes within Allergic Asthma.

Background: Asthma is a heterogeneous chronic disease with different clinical expressions and responses to treatment. In recent years, several unbiased approaches based on clinical, physiological, and molecular features have described several phenotypes of asthma. Some phenotypes are allergic, but little is known about whether these phenotypes can be further subdivided.

PTGDR gene expression and response to dexamethasone treatment in an in vitro model.

Asthma is a multifactorial pathology influenced by environmental and genetic factors. Glucocorticoid treatment decreases symptoms by regulating genes involved in the inflammatory process through binding to specific DNA sequences. Polymorphisms located in the promoter region of the Prostaglandin D Receptor (PTGDR) gene have been related to asthma.

Mouse Models Applied to the Research of Pharmacological Treatments in Asthma.

Models developed for the study of asthma mechanisms can be used to investigate new compounds with pharmacological activity against this disease. The increasing number of compounds requires a preclinical evaluation before starting the application in humans. Preclinical evaluation in animal models reduces the number of clinical trials positively impacting in the cost and in safety.

General and Specific Mouse Models for Asthma Research.

To study the complexity of human asthma disease, the development of different animal models is needed. Among all different laboratory animals, mice represent a useful tool for the development of asthma. This chapter will describe protocols for designing different animal models applied to the studying of asthma phenotypes.

Review of Mouse Models Applied to the Study of Asthma.

The diversity of asthma phenotypes increases its complexity. Animal models represent a useful tool to elucidate the pathophysiological mechanisms involved in both allergic and nonallergic asthma, as well as to identify potential targets for the development of new treatments. Among all available animal models, mice offer significant advantages for the study of asthma.

Promoter Assay Using Luciferase Reporter Gene in the A549 Cell Line.

The development of reporters systems has simplified the study of promoter activity in different areas of knowledge, and represents an easy and fast approach to study genetic variations. In this chapter, we show a transfection protocol of A549 lung epithelial cells with a reporter vector, using the Luciferase-Renilla dual system for studying the variations caused by several polymorphisms in the promoter region of a gene.

Protocol for Lipid-Mediated Transient Transfection in A549 Epithelial Lung Cell Line.

Trials of transfection in eukaryotic cells are essential tools for the study of gene and protein function. They have been used in a wide range of research fields. In this chapter, a method of transient transfection of the A549 cell line, human lung cells of alveolar epithelium, with an expression plasmid is described.

Cell Culture Techniques: Corticosteroid Treatment in A549 Human Lung Epithelial Cell.

Experimentation with cell cultures is widespread in different areas of basic science as well as in the development of biotechnology applied to medicine. Cellular models are applied to the study of respiratory diseases. In this chapter, we present a protocol of basic cell culture using A549 Human lung adenocarcinoma epithelial cells as model.