Increased TSPO expression, pyroglutamate-modified amyloid beta (AßN3(pE)) accumulation and transient clustering of microglia in the thalamus of Tg-SwDI mice.

Epidemiological studies showed that Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) frequently co-occur; however, the precise mechanism is not well understood. A unique animal model (Tg-SwDI mice) was developed to investigate the early-onset and robust accumulation of both parenchymal and vascular Aß in the brain. Tg-SwDI mice have been extensively used to study the mechanisms of cerebrovascular dysfunction, neuroinflammation, neurodegeneration, and cognitive decline observed in AD/CAA patients and to design biomarkers and therapeutic strategies. In the present study, we documented interesting new features in the thalamus of Tg-SwDI mice: 1) a sharp increase in the expression of ionized calcium-binding adapter molecule 1 (Iba-1) in microglia in 6-month-old animals; 2) microglia clustering at six months that disappeared in old animals; 3) N-truncated/modified AßN3(pE) peptide in 9-month-old female and 12-month-old male mice; 4) an age-dependent increase in translocator protein (TSPO) expression. These findings reinforce the versatility of this model for studying multiple pathological issues involved in AD and CAA.

Prevention of recurrent respiratory infections : Inter-society Consensus.

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.

Pidotimod and Immunological Activation in Individuals Infected with HIV.

BACKGROUND: The improvements in HIV infection therapy and the large availability of antiretroviral drugs have led to an increased survival among HIV infected people, and simultaneously to a raised morbidity and mortality due to not-AIDS-related events in this group compared to the general population. An increased systemic inflammation and a persistent immune activation play a pivotal role in determining high rates of non-AIDS comorbidities. In the last years, many natural or synthetic immunomodulatory molecules acting by different mechanisms have been conceived. Pidotimod is a synthetic dipeptide molecule showing immunomodulatory properties. The aim of this pilot study was to evaluate the effects of Pidotimod supplementation on residual inflammation in HIV infected population. METHODS: Forty HIV positive individuals under cART were enrolled: 30 were treated with Pidotimod supplementation (study group) and 10 served as control group (without Pidotimod supplementation). For all participants, Cystatin C, PCR, ESR, microalbuminuria, TNF-α, INF-γ, IL-4, IL-10, IL1ß, IL-18 and IL-2 were measured at enrolment (T0), 4 weeks after of Pidotimod supplementation (T1), and 4 weeks after completing supplementation (T2). RESULTS: In HIV positive participants treated with Pidotimod, the evaluation of cytokine levels showed that IL-10, IFN gamma, and IL-4 were significantly higher at enrolment compared to the control group. The increase under Pidotimod treatment persisted after supplementation suspension, while the pro-inflammatory cytokines levels were reduced. Salivary IgA also increased during 4 weeks of supplementation and persisted at 4 weeks after completing supplementation. On the other hand, the Cystatin C and microalbuminuria levels decreased over time, at a greater extent the Cystatin C serum levels. CONCLUSION: The study findings showed that the HIV population receiving Pidotimod achieved a rebalancing of pro-inflammatory and anti-inflammatory cytokines as well as a significant reduction in cystatin C levels. The treatment further allowed for an increase in salivary IgA levels at all the analyzed times, as a secondary event to a remodulation of the immunological status obtained with pidotimod. This approach could represent a new way to design new intervention strategies aimed at improving the persistent immune activation status in the virologically suppressed HIV population.

Headaches and Magnesium: Mechanisms, Bioavailability, Therapeutic Efficacy and Potential Advantage of Magnesium Pidolate.

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.

Pidotimod in allergic diseases.

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.

Pidotimod enhanced the anti-growth effect of cisplatin on lung cancer in mice via promoting anti-tumor immune response.

Cisplatin-based chemotherapeutics represent a mainstay of lung cancer therapy, but resistance limits their curative potential. In the current study, we reported that Pidotimod, which is an immunostimulant and used for the prevention of acute respiratory infections, elevated cisplatin sensitivity, leading to the synergistic attenuation of tumor growth in mouse lewis lung cancer (LLC) model. With further exploration, we found that Pidotimod enhanced the anti-growth effect of cisplatin on LLC via promoting anti-tumor response, such as increased infiltration of dendrite cells (DCs) and CD8+ T cells as well as enhancement of IFN-γ and Granzyme B expression. In summary, Pidotimod affects the anti-tumor function of cisplatin via promoting anti-tumor immune response and these findings provide a novel approach for the development of therapeutic strategies for lung cancer.

Effects of Pidotimod on recurrent respiratory infections in children with Down syndrome: a retrospective Italian study.

BACKGROUND: Children with Down syndrome (DS) show a high susceptibility to recurrent infections (RI), caused by immune defects and abnormalities of the airways. Our goal was to investigate the effects of Pidotimod on RI prevention in children with DS, comparing immune and clinical parameters before (T0) and after (T1) the treatment with Pidotimod. METHODS: The study was conducted at the Down syndrome outpatient Center of Bambino Gesù Children's Hospital, in Rome. We reviewed the medical records of all children with a positive history for RI and who received oral prophylaxis of Pidotimod from September 2016 to February 2017. RESULTS: Thirty-three children met the inclusion criteria (males: 51.5%; average age: 6 years ±SD: 3). We found a significant decrease in the number of children with upper respiratory infections (82% at T0 vs 24% at T1; p = 0,0001) and with lower respiratory infections (36% at T0 vs 9% at T1; p = 0.003) after treatment with Pidotimod. We also demonstrated a significant decrease in the number of children hospitalized for respiratory infections (18% at T0 vs 3% at T1; p = 0.03). We measured T and B cells in the peripheral blood and B cell function in vitro at T0 and T1. We found that the response to CpG improved at T1. A significant increase of B cell frequency (p = 0.0009), B cell proliferation (p = 0.0278) and IgM secretion (p = 0.0478) were observed in children with DS after treatment. CONCLUSIONS: Our results provided evidence that Pidotimod may be able to prevent RI in children with Down syndrome.

Effects of pidotimod and bifidobacteria mixture on clinical symptoms and urinary metabolomic profile of children with recurrent respiratory infections: a randomized placebo-controlled trial.

BACKGROUND: Many preschool children develop recurrent respiratory tract infections (RRI). Strategies to prevent RRI include the use of immunomodulators as pidotimod or probiotics, but there is limited evidence of their efficacy on clinical features or on urine metabolic profile. OBJECTIVE: To evaluate whether pidotimod and/or bifidobacteria can reduce RRI morbidity and influence the urine metabolic profile in preschool children. MATERIALS AND METHODS: Children aged 3-6 years with RRI were enrolled in a four-arm, exploratory, prospective, randomized, double-blinded, placebo-controlled trial. Patients were randomly assigned to receive pidotimod plus bifidobacteria, pidotimod plus placebo, bifidobacteria plus placebo or double placebo for the first 10 days of each month over 4 consecutive months. Respiratory symptoms and infections were recorded with a daily diary by parents during the study. Metabolomic analyses on urine samples collected before and after treatment were performed. RESULTS: Compared to placebo, children receiving pidotimod, alone or with bifidobacteria, had more symptom-free days (69 versus 44, p = 0.003; and 65 versus 44, p = 0.02, respectively) and a lower percentage of days with common cold (17% versus 37%, p = 0.005; and 15% versus 37%, p = 0.004, respectively). The metabolomic analysis showed that children treated with Pidotimod (alone or in combination with bifidobacteria) present, respect to children treated with placebo, a biochemical profile characterized by compounds related to the pathway of steroids hormones, hippuric acid and tryptophan. No significant difference in the metabolic profile was found between children receiving bifidobacteria alone and controls. CONCLUSIONS: Preschool children with RRI treated with pidotimod have better clinical outcomes and a different urine metabolomic profile than subjects receiving placebo. Further investigations are needed to clarify the connection between pidotimod and gut microbiome.

Pidotimod, an immunostimulant in pediatric recurrent respiratory tract infections: A meta-analysis of randomized controlled trials.

OBJECTIVES: Recurrent respiratory tract infections (RRTIs) remain a great challenge to pediatricians, because they can increase the risk of various complications and there is no confirmed effective treatment. In the present study, we aimed to assess the effectiveness and safety of pidotimod (PDT), an immunostimulant, in treatment of RRTIs in children aged 14 years and under. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials.gov, CBM and CNKI were searched from their inception up to February 2018. All randomized controlled trials (RCTs) using PDT with various treatment durations and enrolling participants <14 years of age were included in the present review. The interventions were PDT plus conventional treatment (e.g. anti-bacterial and antiviral therapy) or PDT alone versus the conventional treatment plus placebo or conventional treatment alone. RESULTS: A total of 29 RCTs consisting of 4344 pediatric patients were included in this meta-analysis. Ten RCTs were published from Italy, Russia or Greece, and 19 RCTs were published by Chinese groups. However, appropriate randomization methods were only used in 15 trials. Only one study had explicit allocation concealment. Since only eight RCTs were double-blind and placebo controlled, the evidence was not assessed as high quality. The meta-analysis indicates that treatment with PDT resulted in a significant increase in the proportion of participants who had lower RTIs (RR 1.59; 95% CI 1.45-1.74, p < 0.00001) compared with the conventional treatment. PDT could significantly decrease the duration of cough and fever. The number of patients in using antibiotics was also remarkably decreased in the PDT treatment group. Moreover, PDT administration improved the levels of serum immunoglobulin (IgG, IgA, or IgM) and T-lymphocyte subtypes (CD3+, CD4+). Besides, PDT administration did not increase the risk of adverse events of any cause (RR = 1.05, 95% CI 0.72-1.54, p = 0.80). CONCLUSIONS: PDT showed a good efficacy and safety in treatment of pediatric RRTIs. Further high-quality and large-scale RCTs are still required to provide confirmatory evidence. TRIAL REGISTRATION: The protocol of this study can be found at PROSPERO with the registration number of CRD42018093541.

Review article: pharmacotherapy for alcohol dependence - the why, the what and the wherefore.

BACKGROUND: The development of alcohol dependence is associated with significant morbidity and mortality. For the majority of affected people the most appropriate goal, in terms of drinking behaviour, is abstinence from alcohol. Psychosocial intervention is the mainstay of the treatment but adjuvant pharmacotherapy is also available and its use recommended. AIM: To provide an updated analysis of current and potential pharmacotherapeutic options for the management of alcohol dependence. In addition, factors predictive of therapeutic outcome, including compliance and pharmacogenetics, and the current barriers to treatment, including doctors' unwillingness to prescribe these agents, will be explored. METHODS: Relevant papers were selected for review following extensive, language- and date-unrestricted, electronic and manual searches of the literature. RESULTS: Acamprosate and naltrexone have a substantial evidence base for overall efficacy, safety and cost-effectiveness while the risks associated with the use of disulfiram are well-known and can be minimised with appropriate patient selection and supervision. Acamprosate can be used safely in patients with liver disease and in those with comorbid mental health issues and co-occurring drug-related problems. A number of other agents are being investigated for potential use for this indication including: baclofen, topiramate and metadoxine. CONCLUSION: Pharmacotherapy for alcohol dependence has been shown to be moderately efficacious with few safety concerns, but it is substantially underutilised. Concerted efforts must be made to remove the barriers to treatment in order to optimise the management of people with this condition.

Effectiveness of 5-Pyrrolidone-2-carboxylic Acid and Copper Sulfate Pentahydrate Association against Drug Resistant Staphylococcus Strains.

Bacterial resistance is an ongoing challenge for pharmacotherapy and pharmaceutical chemistry. Staphylococcus aureus is the bacterial species which makes it most difficult to treat skin and soft tissue infections and it is seen in thousands of hospitalization cases each year. Severe but often underrated infectious diseases, such as complicated nasal infections, are primarily caused by MRSA and S. epidermidis too. With the aim of studying new drugs with antimicrobial activity and effectiveness on drug resistant Staphylococcus strains, our attention in this study was drawn on the activity of a new association between two natural products: 5-pyrrolidone-2-carboxylic acid (PCA), naturally produced by certain Lactobacillus species, and copper sulfate pentahydrate (CS). The antimicrobial susceptibility test was conducted taking into account 12 different Staphylococcus strains, comprising 6 clinical isolates and 6 resistant strains. PCA 4%, w/w, and CS 0.002%, w/w, association in distilled water solution was found to have bactericidal activity against all tested strains. Antimicrobial kinetics highlighted that PCA 4%, w/w, and CS 0.002% association could reduce by 5 log10 viable bacterial counts of MRSA and oxacillin resistant S. epidennidis in less than 5 and 3 minutes respectively. Microscopic investigations suggest a cell wall targeting mechanism of action. Being very safe and highly tolerated, the natural product PCA and CS association proved to be a promising antimicrobial agent to treat Staphylococcus related infections.

Effects of a dragonfly (Anax i.) homeopathic remedy on learning, memory and cell morphology in mice.

BACKGROUND: Homeopathy is a form of alternative medicine in which uses highly diluted preparations that are believed to cause healthy people to exhibit symptoms similar to those exhibited by patients. The aim of this study was to investigate the effects of dragonfly (Anax imperator, Anax i.) on learning and memory in naive mice using the Morris water maze (MWM) test; moreover, the effects of dragonfly on MK-801-induced cognitive dysfunction were evaluated. METHODS: Male balb-c mice were treated with dragonfly (30C and 200C) or MK-801 (0.2 mg/kg) alone or concurrently (n = 10). Dragonfly (D) and MK-801 were administered subchronically for 6 days intraperitoneally 60 min and 30 min, respectively, before the daily performance of the MWM test. RESULTS: This study revealed that in the familiarization session and first session of the MWM test, Anax i. D30 significantly decreased escape latency compared to the control group, although MK-801, D30 and D200 significantly increased escape latency at the end of five acquisition sessions. Anax i. combined with dizocilpine maleate (MK-801) also significantly decreased escape latency in the familiarization session and first session of the MWM test, although this combination increased escape latency compared to the MK-801 alone group at the end of the test. Time spent in escape platform's quadrant in the probe trial significantly decreased while mean distance to platform significantly increased in MK-801, D30 and D200 groups. In the MWM test, Anax i. combined with MK-801 significantly decreased speed of the animals compared to the MK-801 alone group. General cell morphology was disturbed in the MK-801 group while D30 and D200 seemed to improve cell damage in the MK-801 group. CONCLUSIONS: These results suggest that the homeopathic Anax i. can impair learning acquisition and reference memory, and it has beneficial effects on disturbed cell morphology.

Immunomodulatory activity of pidotimod administered with standard antibiotic therapy in children hospitalized for community-acquired pneumonia.

BACKGROUND: Several attempts to improve immune function in young children have been made and encouraging results have been collected with pidotimod (PDT), a synthetic dipeptide molecule that seems to have immunomodulatory activity on both innate and adaptive responses. Until now, the effects of PDT on the immune system have only been studied in vivo after long-term administration to evaluate whether its immunomodulatory activity might prevent the development of infections. This study was planned to evaluate the immunomodulatory activity of PDT administered together with standard antibiotic therapy in children hospitalized for community-acquired pneumonia (CAP). METHODS: A total of 20 children hospitalized for community-acquired pneumonia (CAP) were randomized at a 1:1 ratio to receive either standard antibiotics plus pidotimod (PDT) or standard antibiotics alone to evaluate the immunomodulatory activity of PDT. Blood samples for the evaluation of immunological parameters were drawn at the time of recruitment (T0) (i.e., before therapy administration), at T3 and T5 (i.e., 3 and 5 days after the initiation of therapy) as well as at T21 (i.e., 7 days after the therapy ended). RESULTS: Following pneumococcal polysaccharide stimulation, the percentage of dendritic cells (DCs) expressing activation and costimulatory molecules was significantly higher in children receiving PDT plus antibiotics than in the controls. A significant increase in tumor necrosis factor-α and/or interleukin-12 secretion and expression of toll like receptor 2 was observed in PDT-treated children compared with controls; this was followed by an increased release of proinflammatory cytokines by monocytes. In the PDT-treated group, mRNA expression of antimicrobial peptides and genes involved in the inflammatory response were also augmented in comparison with the controls. CONCLUSIONS: These results demonstrate, for the first time, that PDT administered together with standard antibiotics is associated with a favorable persistent immunomodulatory effect in children with CAP.

[Effectiveness of pidotimod in combination with bacterial lysates in the treatment of the pfapa (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome]. / Efficacia del Pidotimod in associazione a lisato batterico nel trattamento della syndrome PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis).

AIM: PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome is the most common autoinflammatory syndrome in pediatrics, accepted as an hyperimmune condition. Pidotimod is a molecule with immunomodulatory activity on both innate and adaptive immune responses; it also has the capacity to modulate the function of the respiratory epithelial cells through the activation of a NK-KB pathway which would involve the host-virus interaction. Moreover, the proven beneficial effect of Pidotimod in enhancing the immune response during vaccination, and its benefits in the prevention of respiratory tract infections, should be noted. METHODS: A joint combination of Pidotimod and bacterial lysates was used to treat 37 children with a clinical diagnosis of PFAPA; within the end of the first year of therapy, the healing rate of PFAPA symptoms was 67.5% (25 children), with a 10.8% (4 cases) still in complete remission within the end of the second year of follow-up. RESULTS: It is important to highlight that 29 children (78.3%) had benefitted from this therapy, in terms of healing, with a marked decrease in the incidence of fever from a total of 360 to 106 episodes, and episodes of periodic fever occurring almost 4 times less frequently. The use of Pidotimod determined a significant reduction of surgical tonsillectomy's treatment. CONCLUSION: This approach had a strong impact on the children's quality of life; a significant decrement in the use of antipyretic drugs, as well as a lower rate of antibiotic prescription, were also noted. It also had a dramatic impact on families' lives, because the treatment lowers the number of absences of family members from work or school/kindergarten.

Pidotimod for the prevention of acute respiratory infections in healthy children entering into daycare: A double blind randomized placebo-controlled study.

Acute respiratory tract infections (ARTIs) are very common in pediatric age and reach a peak in the first 4 years of life, especially in children attending daycare. Pidotimod, a synthetic immunostimulant, may reduce the incidence of ARTIs in children with predisposing risk factors. Nevertheless studies on healthy children are presently lacking. We performed a double-blinded randomized placebo-controlled trial study to assess the efficacy of Pidotimod in a population of 3-year-old healthy children who just entered kindergarten. The main outcome was the incidence of respiratory infections in this population and the secondary outcome was the prescription of antibiotics. The study group consisted of healthy 3-year-old children who had not yet attended day-care centers. Patients were enrolled by a convenience sample of 17 family pediatricians (FP). Children were randomized to receive either Pidotimod 400 mg per os or placebo twice daily for the last 10 days of each month from October 2013 to April 2014. Any time a child presented to his/her FP with fever and ARTI was diagnosed, clinical and therapeutic data were collected. A total of 800 children were pre-screened, 733 did not meet the inclusion criteria and 10 refused to participate. Of the 67 eligible subjects, 57 were successfully enrolled within the study recruitment period and randomized to receive Pidotimod (n = 29) or placebo (n = 28). Eight children were lost to follow-up. In the final analysis were thus included 24 children who received Pidotimod and 25 who received placebo. The incidence rate ratio for respiratory infections was 0.78 (95%CI 0.53 to 1.15, p = 0.211) for Pidotimod vs. placebo. The corresponding risk ratio for antibiotic usage was 0.56 (95%CI 0.27 to 1.16, p = 0.120). In our trial, Pidotimod did not prove to be statistically superior to placebo for the prevention of ARTI in a population of healthy children who entered kindergarten. However, Pidotimod showed some potential as a means for reducing antibiotic usage in these children.

Efficacy and safety of pidotimod in the prevention of recurrent respiratory infections in children: a multicentre study.

Acute respiratory infections (ARI) still represent a big challenge for paediatricians, especially in those children defined as "ailed" as they are more susceptible to such kinds of disease. In this paediatric population, the immune system is still under-developed with an evident alteration in cytokine levels. A clinical study was carried out in 5 sites in Russia with the intention to enroll children particularly susceptible to contract respiratory infections (defined as "ailing"), assigning them to a treatment group with pidotimod in comparison with a control group, treating them for 30 days and observing the reduction in the number of ARI episodes throughout the follow-up period (6 months). Moreover, changes in serum immunological markers were evaluated at baseline and 30 days after treatment discontinuation. One hundred and fifty-seven ailing children were enrolled and assigned to two arms: a main pidotimod treatment group or a control group. The percentage of incidence of ARIs in the observation period at three different time points was statistically significant (p < 0.05). At the end of the follow-up period (after 6 months), ARIs had developed in 72 children (92.3%) in the main group and in 79 patients (100%) in the control group. Concerning changes of the immunological markers, the treatment group showed a better profile of normalization compared to the control group. The 30-day pidotimod therapy course led to improvement/reduction in the rate of acute respiratory infection recurrence in ailing children within a 3-month period, with a quick elimination of symptoms and signs of infection and, as a result, a faster recovery. The normalisation of the content of the pro-inflammatory cytokine interleukin-8 confirmed the immune-modulatory effect of the investigational drug, underlying its prophylactic effect.

Pidotimod may prevent recurrent respiratory infections in children.

AIM: Recurrent respiratory infections (RRI) constitute a social problem for both the pharmaco-economic impact and the burden for the family. Pidotimod is a synthetic immunostimulant. The aim of this study was to evaluate the effects of pidotimod on RRI prevention in children. METHODS: Globally, 100 children (49 males, mean age 4.7 ± 1.2 years) with RRI were enrolled in the study. At baseline, children were randomly assigned to the treatment with pidotimod 400 mg/die or not for two months. Children were visited at baseline, after 30 (T1) and 60 (T2) days, and at follow-up (120 days; T3). Number of children with upper and lower airways symptoms, medications use, school attendance, and paediatric visits for RRI were evaluated. RESULTS: Pidotimod treatment was able of significantly reducing the number of children with upper and lower airways symptoms, and medications use, increasing school attendance, and reducing pediatric visits for RRI. CONCLUSION: This study provided the evidence that pidotimod may be able of preventing RRI in children.

Pidotimod: the past and the present.

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.

Immunostimulants and prevention of recurrent respiratory tract infections.

Recurrent respiratory tract infections (RRTIs) are very common in children and a major challenge for pediatricians. They affect the children's quality of life, cause absences from school and lost parental working days, and repeated medical examinations, hospital admissions as well as antibiotic therapies lead to high costs for society. Given their prevalence and clinical importance, various prevention strategies have been developed. One of the most widely used is the administration of immunostimulants: i.e. molecules of bacterial or synthetic origin that interact with immunological mechanisms in vitro and in vivo. A number of studies have investigated their effects on cellular and innate immunity, and their clinical efficacy, but there is no consensus as to their real usefulness. The main aim of this review is to analyse the available data concerning the activity and efficacy of immunostimulants in preventing pediatric RRTIs. The majority of studies have shown that the number of infections decreases after immunostimulant treatment, but they are affected by various methodological weaknesses. Further studies are urgently needed to confirm whether, when and which immunostimulants should be used.