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Italian Journal of Pediatrics Oct 2021Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first...
Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.
Topics: Adenoidectomy; Adjuvants, Immunologic; Administration, Intranasal; Algorithms; Antibiotic Prophylaxis; Antioxidants; Child; Complementary Therapies; Humans; Hyaluronic Acid; Influenza Vaccines; Pneumococcal Vaccines; Prebiotics; Probiotics; Pyrrolidonecarboxylic Acid; Recurrence; Respiratory Tract Infections; Resveratrol; Thiazolidines; Tonsillectomy; Vitamins
PubMed: 34696778
DOI: 10.1186/s13052-021-01150-0 -
Nutrients Aug 2020Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a... (Review)
Review
Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines. A number of double-blind randomized placebo-controlled trials have shown that magnesium is efficacious in relieving headaches and have led to the recommendation of oral magnesium for headache relief in several national and international guidelines. Among several magnesium salts available to treat magnesium deficiency, magnesium pidolate may have high bioavailability and good penetration at the intracellular level. Here, we discuss the cellular and molecular effects of magnesium deficiency in the brain and the clinical evidence supporting the use of magnesium for the treatment of headaches and migraines.
Topics: Administration, Oral; Biological Availability; Dietary Supplements; Headache; Humans; Magnesium; Magnesium Deficiency; Migraine Disorders; Pyrrolidonecarboxylic Acid; Randomized Controlled Trials as Topic
PubMed: 32878232
DOI: 10.3390/nu12092660 -
JAMA Neurology Oct 2022β-amyloid plaques and neurofibrillary tau deposits biologically define Alzheimer disease. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
β-amyloid plaques and neurofibrillary tau deposits biologically define Alzheimer disease.
OBJECTIVE
To perform post hoc analyses of amyloid reduction after donanemab treatment and assess its association with tau pathology and clinical measures.
DESIGN, SETTING, AND PARTICIPANTS
The Study of LY3002813 in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ) was a phase 2, placebo-controlled, randomized clinical trial conducted from December 18, 2017, to December 4, 2020, with a double-blind period of up to 76 weeks and a 48-week follow-up period. The study was conducted at 56 centers in the US and Canada. Enrolled were participants from 60 to 85 years of age with gradual and progressive change in memory function for 6 months or more, early symptomatic Alzheimer disease, elevated amyloid, and intermediate tau levels.
INTERVENTIONS
Donanemab (an antibody specific for the N-terminal pyroglutamate β-amyloid epitope) dosing was every 4 weeks: 700 mg for the first 3 doses, then 1400 mg for up to 72 weeks. Blinded dose-reduction evaluations occurred at 24 and 52 weeks based on amyloid clearance.
MAIN OUTCOMES AND MEASURES
Change in amyloid, tau, and clinical decline after donanemab treatment.
RESULTS
The primary study randomized 272 participants (mean [SD] age, 75.2 [5.5] years; 145 female participants [53.3%]). The trial excluded 1683 of 1955 individuals screened. The rate of donanemab-induced amyloid reduction at 24 weeks was moderately correlated with the amount of baseline amyloid (Spearman correlation coefficient r, -0.54; 95% CI, -0.66 to -0.39; P < .001). Modeling provides a hypothesis that amyloid would not reaccumulate to the 24.1-centiloid threshold for 3.9 years (95% prediction interval, 1.9-8.3 years) after discontinuing donanemab treatment. Donanemab slowed tau accumulation in a region-dependent manner as measured using neocortical and regional standardized uptake value ratios with cerebellar gray reference region. A disease-progression model found a significant association between percentage amyloid reduction and change on the integrated Alzheimer Disease Rating Scale only in apolipoprotein E (APOE) ε4 carriers (95% CI, 24%-59%; P < .001).
CONCLUSIONS AND RELEVANCE
Results of post hoc analyses for donanemab-treated participants suggest that baseline amyloid levels were directly associated with the magnitude of amyloid reduction and inversely associated with the probability of achieving complete amyloid clearance. The donanemab-induced slowing of tau was more pronounced in those with complete amyloid clearance and in brain regions identified later in the pathologic sequence. Data from other trials will be important to confirm aforementioned observations, particularly treatment response by APOE ε4 status.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03367403.
Topics: Aged; Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Amyloidosis; Apolipoprotein E4; Epitopes; Female; Humans; Infant; Plaque, Amyloid; Positron-Emission Tomography; Pyrrolidonecarboxylic Acid; tau Proteins
PubMed: 36094645
DOI: 10.1001/jamaneurol.2022.2793 -
Nature Medicine Apr 2019Cancer cells can evade immune surveillance through the expression of inhibitory ligands that bind their cognate receptors on immune effector cells. Expression of...
Cancer cells can evade immune surveillance through the expression of inhibitory ligands that bind their cognate receptors on immune effector cells. Expression of programmed death ligand 1 in tumor microenvironments is a major immune checkpoint for tumor-specific T cell responses as it binds to programmed cell death protein-1 on activated and dysfunctional T cells. The activity of myeloid cells such as macrophages and neutrophils is likewise regulated by a balance between stimulatory and inhibitory signals. In particular, cell surface expression of the CD47 protein creates a 'don't eat me' signal on tumor cells by binding to SIRPα expressed on myeloid cells. Using a haploid genetic screen, we here identify glutaminyl-peptide cyclotransferase-like protein (QPCTL) as a major component of the CD47-SIRPα checkpoint. Biochemical analysis demonstrates that QPCTL is critical for pyroglutamate formation on CD47 at the SIRPα binding site shortly after biosynthesis. Genetic and pharmacological interference with QPCTL activity enhances antibody-dependent cellular phagocytosis and cellular cytotoxicity of tumor cells. Furthermore, interference with QPCTL expression leads to a major increase in neutrophil-mediated killing of tumor cells in vivo. These data identify QPCTL as a novel target to interfere with the CD47 pathway and thereby augment antibody therapy of cancer.
Topics: Aminoacyltransferases; Animals; Antigens, Differentiation; CD47 Antigen; Cell Line, Tumor; Cell Membrane; Humans; Immunotherapy; Mice, Transgenic; Neoplasms; Opsonin Proteins; Pyrrolidonecarboxylic Acid; Receptors, Immunologic
PubMed: 30833751
DOI: 10.1038/s41591-019-0356-z -
Frontiers in Cellular and Infection... 2022Kidney stones or nephrolithiasis is a chronic metabolic disease characterized by renal colic and hematuria. Currently, a pathogenetic mechanism resulting in kidney stone...
BACKGROUND
Kidney stones or nephrolithiasis is a chronic metabolic disease characterized by renal colic and hematuria. Currently, a pathogenetic mechanism resulting in kidney stone formation remains elusive. We performed a multi-omic study investigating urinary microbial compositions and metabolic alterations during nephrolithiasis.
METHOD
Urine samples from healthy and individuals with nephrolithiasis were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectroscopy. Microbiome and metabolome profiles were analyzed individually and combined to construct interactome networks by bioinformatic analysis.
RESULTS
Distinct urinary microbiome profiles were determined in nephrolithiasis patients compared with controls. Thirty-nine differentially abundant taxa between controls and nephrolithiasis patients were identified, and Streptococcus showed the most significant enrichment in nephrolithiasis patients. We also observed significantly different microbial compositions between female and male nephrolithiasis patients. The metabolomic analysis identified 112 metabolites that were differentially expressed. Two significantly enriched metabolic pathways, including biosynthesis of unsaturated fatty acids and tryptophan metabolism, were also identified in nephrolithiasis patients. Four potentially diagnostic metabolites were also identified, including trans-3-hydroxycotinine, pyroglutamic acid, O-desmethylnaproxen, and FAHFA (16:0/18:2), and could function as biomarkers for the early diagnosis of nephrolithiasis. We also identified three metabolites that contributed to kidney stone size. Finally, our integrative analysis of the urinary tract microbiome and metabolome identified distinctly different network characteristics between the two groups.
CONCLUSIONS
Our study has characterized important profiles and correlations among urinary tract microbiomes and metabolomes in nephrolithiasis patients for the first time. These results shed new light on the pathogenesis of nephrolithiasis and could provide early clinical biomarkers for diagnosing the disease.
Topics: Biomarkers; Female; Humans; Kidney; Kidney Calculi; Male; Pyrrolidonecarboxylic Acid; RNA, Ribosomal, 16S; Tryptophan
PubMed: 36132987
DOI: 10.3389/fcimb.2022.953392 -
Minerva Pediatrica Oct 2020The rising incidence of allergic disease requires more specific, effective and safe therapeutic strategies. In this regard, several kinds of biologically active... (Review)
Review
The rising incidence of allergic disease requires more specific, effective and safe therapeutic strategies. In this regard, several kinds of biologically active substances, commonly known as immunostimulants, have been introduced for the prevention and treatment of allergic diseases in pediatric population. Among the heterogeneous group of biologically active molecules to date available, pidotimod (Axil, Valeas S.p.A, Milan) is proved to be able to ameliorate both innate and adaptive immunity and enhances the immune system properties often impaired in patients with allergic disorders.
Topics: Adaptive Immunity; Adjuvants, Immunologic; Adolescent; Asthma; Child; Child, Preschool; Chronic Urticaria; Dermatitis, Atopic; Desensitization, Immunologic; Food Hypersensitivity; Humans; Hypersensitivity; Immunity, Innate; Immunologic Factors; Pyrrolidonecarboxylic Acid; Rhinitis, Allergic; Thiazolidines
PubMed: 32731733
DOI: 10.23736/S0026-4946.20.05967-8 -
International Journal of... 2009Pidotimod (Polimod ) is a synthetic dipeptide molecule with biological and immunological activity on both the adaptive and the innate immune responses. In vitro studies,... (Review)
Review
Pidotimod (Polimod ) is a synthetic dipeptide molecule with biological and immunological activity on both the adaptive and the innate immune responses. In vitro studies, both from animal and human specimens, have documented a good activity on innate and adaptive immune responses and have been confirmed by in vivo studies. These activities have been applied in clinical studies demonstrating the efficacy of pidotimod in reducing the rate of recurrent infections of the upper respiratory and urinary tracts in children. The same results were obtained in recurrent respiratory tract infections in adults. Interestingly, these effects are more evident in the setting of immune defects such as senescence, Downs syndrome, and cancer.
Topics: Adjuvants, Immunologic; Adult; Animals; Child; Humans; Immunity, Innate; Pyrrolidonecarboxylic Acid; Recurrence; Respiratory Tract Infections; Thiazolidines; Treatment Outcome; Urinary Tract Infections
PubMed: 19505378
DOI: 10.1177/039463200902200201 -
Critical Care (London, England) May 2019
Topics: Aged; Cerebrovascular Circulation; Critical Illness; Female; Glutathione; Homeostasis; Humans; Male; Middle Aged; Oxidative Stress; Prospective Studies; Pyrrolidonecarboxylic Acid; Shock, Septic; Spain
PubMed: 31064383
DOI: 10.1186/s13054-019-2454-1 -
The Biochemical Journal Jul 1973A new procedure for the qualitative and quantitative determination of asparagine, glutamine and pyrrolidonecarboxylic acid in total enzymic hydrolysates of peptides and...
A new procedure for the qualitative and quantitative determination of asparagine, glutamine and pyrrolidonecarboxylic acid in total enzymic hydrolysates of peptides and glycopeptides based on g.l.c. has been developed. Under the conditions of esterification and trifluoroacetylation N-trifluoroacetylaspartic acid mono-n-butyl ester was formed from asparagine and N-trifluoroacetylglutamic acid mono-n-butyl ester from both glutamine and pyrrolidonecarboxylic acid. To distinguish between the latter two compounds, the esterification was carried out at room temperature yielding 30% of esterified pyrrolidonecarboxylic acid but less than 1% of esterified glutamine. In extending the g.l.c. of amino acids, the previously unknown positions in the g.l.c. elution pattern of the following amino acids could also be reproducibly determined: carboxymethylcysteine, homoserine, hydroxylysine and in-methyl-lysine. Further, certain glycopeptides were investigated and the artifacts due to their carbohydrate moieties were determined.
Topics: Amino Acids; Asparagine; Chromatography, Gas; Enzymes; Esters; Fluoroacetates; Glutamine; Glycopeptides; Homoserine; Hydrolysis; Hydroxylysine; Lysine; Methods; Peptides; Pyrrolidinones; Pyrrolidonecarboxylic Acid
PubMed: 4733240
DOI: 10.1042/bj1330551 -
Italian Journal of Pediatrics Dec 2013At the end of 1990s, acute respiratory tract infections (ARTIs) were called the 'forgotten pandemic', with a clear dichotomy between developing and industrialised... (Comparative Study)
Comparative Study
At the end of 1990s, acute respiratory tract infections (ARTIs) were called the 'forgotten pandemic', with a clear dichotomy between developing and industrialised countries in mortality and morbidity, the main outcomes associated with ARTIs. This definition still applies 20 years later, when the introduction of new and safe antibiotics and vaccines has certainly contributed to controlling the most life-threatening ARTIs, but has not had a major impact on viral ARTIs in paediatric age. One functional approach to preventing and treating ARTIs is non-specifically increasing the immune response or enhancing the children's innate defence mechanisms. Different kinds of biologically active substances--called immunostimulants--of natural and synthetic origins and with different mechanisms of action have been introduced in some countries for the prevention of ARTIs in children. Recently, research focused on one of these compounds, Pidotimod, has attempted to better clarify and define its mechanisms of action both in vitro and in vivo. In this paper, we critically examine the most recent findings on Pidotimod. Certainly the improvement of research methodology in the last 20 years and the acquired knowledge in various fields of clinical immunology should be the starting point for research on Pidotimod. Preclinical research will be essential to better understand the mechanisms of action of this compound. However, in vivo studies, especially randomised control trials, will be necessary to establish the real efficacy of Pidotimod in the prevention of ARTIs in paediatric age.
Topics: Acute Disease; Adaptive Immunity; Adjuvants, Immunologic; Animals; Child; Child, Preschool; Cohort Studies; Disease Models, Animal; Female; Forecasting; Humans; Immunity, Innate; Incidence; Male; Pyrrolidonecarboxylic Acid; Respiratory Tract Infections; Risk Factors; Secondary Prevention; Thiazolidines; Treatment Outcome
PubMed: 24314100
DOI: 10.1186/1824-7288-39-75