How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWH.

High levels of reactive oxygen species (ROS) are present in people living with HIV (PLWH), produced by intense physical activity; in response, our body produces antioxidant molecules. ROS influence the expression of gene-encoding enzymes and transporters involved in drug biotransformation. In addition, pharmacogenetics can influence transporter activity, and thus drug exposure.

Development and Validation of a UHPLC-MS/MS Method for the Simultaneous Quantification of Candesartan and Bisoprolol Together with Other 16 Antihypertensive Drugs in Plasma Samples.

Antihypertensive pharmacological therapy is often characterized by a coadministration of different classes of drugs. Therefore, analytical methods allowing the simultaneous quantification of many drugs are needed for therapeutic drug monitoring (TDM) purposes in this context. In particular, TDM represents a useful tool to discriminate poor adherence from real cases of resistant hypertension.

Extracellular Vesicle-Enclosed Oxidative Stress- and Inflammation-Related microRNAs as Potential Biomarkers of Vitamin D Responsivity: A Pilot Study on Inflammatory Bowel Disease Patients with or without COVID-19.

The relationship between serum 25-hydroxyvitamin D (25(OH)D) levels, genomic response to vitamin D (Vit.D), and positivity to SARS-CoV-2 remains understudied. In this pilot study, during the follow-up of patients with Inflammatory Bowel Disease (IBD) and COVID-19, we investigated this issue by analyzing the molecular contents of serum extracellular vesicles (EVs) from six groups of IBD patients (n = 32), classified according to anti-SARS-CoV-2 status, 25(OH)D level, and Vit.

Studying the Changes in Physical Functioning and Oxidative Stress-Related Molecules in People Living with HIV after Switching from Triple to Dual Therapy.

Background: Physical activity could increase the production of oxidative stress biomarkers, affecting the metabolism and excretion of antiretroviral drugs and, consequently, the clinical outcome. Nowadays, people living with HIV (PLWH) are mostly switching from triple to dual therapy, but no data are available in terms of physical functioning and oxidative stress. The aim of this study was to evaluate if some antioxidant biomarkers and physical functioning tests could be different according to triple or dual antiretroviral therapy.

Plasma, intracellular and lymph node antiretroviral concentrations and HIV DNA change during primary HIV infection: Results from the INACTION P25 study.

Despite its effectiveness, combination antiretroviral treatment (cART) has a limited effect on HIV DNA reservoir, which establishes early during primary HIV infection (PHI) and is maintained by latency, homeostatic T-cells proliferation, and residual replication. This limited effect can be associated with low drug exposure in lymphoid tissues and/or suboptimal adherence to antiretroviral drugs (ARVs). The aim of this study was to assess ARV concentrations in plasma, peripheral blood mononuclear cells (PBMCs) and lymph nodes (LNs), and their association to HIV RNA and HIV DNA decay during PHI.

Pharmacogenetics of tenofovir drug transporters in the context of HBV: Is there an impact?

Background: Current treatments for chronic hepatitis B management include orally administered nucleos(t)ide analogues, such as tenofovir (TDF), which is an acyclic adenine nucleotide analogue used both in HBV and human immune deficiency virus (HIV). The course of HBV infection is mainly dependent on viral factors, such as HBV genotypes, immunological features and host genetic variables, but a few data are available in the context of HBV, in particular for polymorphisms of genes encoding proteins involved in drug metabolism and elimination. Consequently, the aim of this study was to evaluate the potential impact of genetic variants on TDF plasma and urine concentrations in patients with HBV, considering the role of HBV genotypes.

Cannabinoid levels description in a cohort of patients with chronic and neuropathic pain treated with Cannabis decoction: A possible role of TDM.

The phytocomplex of Cannabis is made up of approximately 500 substances: terpeno-phenols metabolites, including Δ-9-tetrahydrocannabinol and cannabidiol, exhibit pharmacological activity. Medical Cannabis has several pharmacological potential applications, in particular in the management of chronic and neuropathic pain. In the literature, a few data are available concerning cannabis pharmacokinetics, efficacy and safety.

Multiple drug intolerance in antihypertensive patients: what is known and what is missing.

Drug allergy and intolerance are increasingly recognized as significant public health concerns, leading to adverse reactions in patients undergoing pharmacological treatments. Multiple drug intolerance syndrome (MDIS), characterized by adverse reactions to at least three different drug classes without a clear immunological mechanism, poses a substantial challenge, particularly in hypertensive patients. Despite its link to suboptimal adherence and uncontrolled blood pressure, MDIS in the context of hypertension remains insufficiently explored.

Therapeutic Drug Monitoring as a Tool for the Clinical Outcome Prediction in Vedolizumab-Treated Patients: An Italian Pilot Study.

Over the years, vedolizumab (VDZ) has emerged as a more effective target therapy for inflammatory bowel disease. The aim of this work was to analyze a cohort of inflammatory bowel disease patients, evaluating the association between VDZ serum concentrations at 6 months from starting therapy and their clinical and biochemical indexes within one year of treatment, correlating drug levels with response and clinical remission. Forty patients treated with VDZ were enrolled.

Comparative Performance Assessment of Novel Fluorescence Immunoassay POCTs for Measuring Circulating Levels of Vitamin-D.

Vitamin D (Vit D) is a fat-soluble molecule acting like a hormone, and it is involved in several biological mechanisms such as gene expression, calcium homeostasis, bone metabolism, immune modulation, viral protection, and neuromuscular functions. Vit D deficiency can lead to chronic hypocalcemia, hyperparathyroidism, and many other pathological conditions; in this context, low and very low levels of 25-hydroxy-vitamin D (25-OH-D) were found to be associated with an increased risk of COVID-19 infection and the likelihood of many severe diseases. For all these reasons, it is important to quantify and monitor 25-OH-D levels to ensure that the serum/blood concentrations are not clinically suboptimal.

Host single nucleotide polymorphisms and biomarkers of neuronal damage and inflammation in people living with HIV.

Objectives: Blood-brain barrier impairment is frequent in people living with human immunodeficiency virus (PLWHIV), affecting the penetration of target cells and antiretrovirals into the central nervous system, through transporters (e.g. ABCB1), leading to neuroinflammation.

Correlation between Polymorphisms of Vitamin D Metabolism Genes and Perianal Disease in Crohn's Disease.

Although the role of vitamin D (VD) in the pathogenesis and progression of Crohn's disease (CD) is known, the association between single-nucleotide polymorphisms (SNPs) of genes linked to vitamin D pathway and CD risk is still under study. Furthermore, no significant association has been previously found between these SNPs and perianal CD (pCD), a severe phenotypic manifestation of CD that may present as perianal fistula, abscess, and recto-vaginal fistula. Among the mechanisms involved in its pathogenesis, local inflammation and intestinal microbiota alteration are recognized.

Stability Study of Fosfomycin in Elastomeric Pumps at 4 °C and 34 °C: Technical Bases for a Continuous Infusion Use for Outpatient Parenteral Antibiotic Therapy.

Background: Fosfomycin acts against aerobic Gram-/+ bacteria by blocking the synthesis of peptidoglycan. Its use has been currently re-evaluated for intravenous administration for the treatment of systemic infections by multidrug-resistant bacteria. Concentration-/time-dependent activity has been suggested, with potential clinical advantages from prolonged or continuous infusion.

Vitamin D impact in affecting clozapine plasma exposure: A potential contribution of seasonality.

Schizophrenia affects approximately 24 million people worldwide and clozapine is the most effective antipsychotic drug. Nevertheless, its use in therapy is limited due to adverse effects.Therapeutic drug monitoring is a clinical tool useful to reduce the clozapine toxicity.

A Novel UHPLC-MS/MS Method for the Quantification of Seven Opioids in Different Human Tissues.

Background: Opioids are considered the cornerstone of pain management: they show good efficacy as a first-line therapy for moderate to severe cancer pain. Since pharmacokinetic/pharmacodynamic information about the tissue-specific effect and toxicity of opioids is still scarce, their quantification in post-mortem autoptic specimens could give interesting insights.

Methods: We describe an ultra-high-performance liquid chromatography coupled with tandem mass spectrometry method for the simultaneous quantification of methadone, morphine, oxycodone, hydrocodone, oxymorphone, hydromorphone and fentanyl in several tissues: liver, brain, kidney, abdominal adipose tissue, lung and blood plasma.

Pro-Environmental Behaviors and Well-Being in Adolescence: The Mediating Role of Place Attachment.

Adolescents represent the future generation, so it is important to pay attention to behaviors that involve them as actors in social activities and constitute the expression of an adequate growth path. Engaging in pro-environmental behaviors leads adolescents to do something good for themselves, for their own community, and for the place in which they live, and this type of conduct increases their levels of well-being and place attachment. This study examines the association between pro-environmental behavior and personal and social well-being in a sample of 1925 adolescents aged 14 to 20 years.

COVID-19: A Possible Contribution of the MAPK Pathway.

Background: COVID-19 is characterized by an uncontrolled inflammatory response with high pro-inflammatory cytokine production through the activation of intracellular pathways, such as mitogen-activated protein kinase (MAPK). Viruses are able to exploit the MAPK pathway to their advantage; this pathway relevance to severe COVID-19 is poorly described. The aim of this study was to quantify biomarkers involved in the MAPK pathway and to clarify its possible role in affecting some COVID-19-related clinical features.

COVID-19: Focusing on the Link between Inflammation, Vitamin D, MAPK Pathway and Oxidative Stress Genetics.

An uncontrolled inflammatory response during SARS-CoV-2 infection has been highlighted in several studies. This seems to be due to pro-inflammatory cytokines whose production could be regulated by vitamin D, ROS production or mitogen-activated protein kinase (MAPK). Several genetic studies are present in the literature concerning genetic influences on COVID-19 characteristics, but there are few data on oxidative stress, vitamin D, MAPK and inflammation-related factors, considering gender and age.

Analytical validation of a novel UHPLC-MS/MS method for 19 antibiotics quantification in plasma: Implementation in a LC-MS/MS Kit.

Background: Therapeutic drug monitoring (TDM) for antibiotic drugs represents a consolidated practice to optimize the effectiveness and to limit the toxicity of specific drugs by guiding dosage adjustments. The comparison of TDM results with drug-specific pharmacokinetic/pharmacodynamic (PK/PD) parameters, based on killing dynamics and bacterial susceptibility, increases the probability of therapeutic success.

Purpose: The aim of this study was the analytical validation of a new UHPLC-MS/MS assay for the quantification of 19 antibiotics divided in two different sets considering their chemical/pharmacological properties.

Antiretroviral Levels in the Cerebrospinal Fluid: The Effect of Inflammation and Genetic Variants.

Neurocognitive impairments are common in people living with HIV. Some conditions, such as chronic inflammation, astrocyte infection and an impaired blood-brain barrier (BBBi), along with host genetic variants in transporter genes, may affect antiretroviral (ARV) exposure in the cerebrospinal fluid (CSF). The aim of this study was to evaluate ARV CSF penetration according to compartmental inflammation, BBB permeability and single-nucleotide polymorphisms (SNPs) in drug transporter encoding genes.

Self-Esteem and Adolescent Bullying/Cyberbullying and Victimization/Cybervictimization Behaviours: A Person-Oriented Approach.

Although previous studies seemed to recognize negative associations between self-esteem and bullying/cyberbullying and victimization/cybervictimization behaviours, the findings are controversial. The current study tried to shed light on this issue by using a person-oriented approach among Italian adolescents. Participants included 936 students aged 13-16 years.

A new UHPLC-MS/MS method for cannabinoids determination in human plasma: A clinical tool for therapeutic drug monitoring.

Cannabinoid derivates have been largely used for different medical purpose. In the literature, several methods capable of separating THC and its principles metabolites are described, although Δ8- and Δ9-THC separation has not been completely achieved. THC metabolism has not been fully understood and metabolites plasma distribution in healthy and pathological patients remains to further deepen.

Cybervictimisation and Well-Being during the Outbreak of COVID-19: The Mediating Role of Depression.

Social distancing during the COVID-19 pandemic contributed to modifying relational habits and increasing Internet use to engage in antisocial behaviours such as cybervictimisation. Additionally, social distancing can reinforce the relationship with internalising behaviours such as depression. Through an adolescent sample, this study examines the relationship between cybervictimisation and well-being and the mediating role of depression.

Pregnancy and COVID-19: The Possible Contribution of Vitamin D.

Background: Vitamin D deficiency has been associated with the severity of COVID-19. The role of vitamin D in pregnant women with COVID-19 has been poorly investigated to date. The aim of this study was to evaluate the influence of vitamin D in affecting some clinical features in pregnancy between SARS-CoV-2 positive and negative patients.

The Relationship between Parental Monitoring, Peer Pressure, and Motivations for Responsible Drinking among Italian Adolescents: The Mediating Role of Positive Alcohol Expectancies.

This study investigated the associations between parental monitoring, peer pressure, and motivations for responsible drinking, while also taking the mediating role of positive alcohol expectancies into account. The participants were 579 Italian adolescents, aged 14-20 years ( = 16.39 years,  = 1.