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Journal articles on the topic 'Pidotimod'

Author: Grafiati

Published: 9 March 2023

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1

Baghel, Madhuri, Meenakshi Bharkatiya, Falguni Tandel, and Sadhana J. Rajput. "Isolation and Characterization of Novel Degradation Product of Pidotimod." Asian Journal of Chemistry 34, no. 9 (2022): 2386–92. http://dx.doi.org/10.14233/ajchem.2022.23878.

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A synthetic dipeptide, pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4-carboxylic acid, PTD) is an immunomodulator and it possesses anti-infective activity against variety of infections. The objective of this study was to explore into and identify pidotimod’s major degradation product. Pidotimod was degraded in ICH prescribed stress conditions. pidotimod was degraded 90% in 1.0 N NaOH at 80 ºC for 6 h and the degradation product (DP2) was determined using HPLC. The HPLC method was used to separate the primary and subsidiary degradation products and carried out on a C18 column with a mobile phase of ammonium acetate buffer (pH 4.5; 10 mM) and MeOH/ACN (90:10 v/v) at a ratio of 97:03 v/v at 40 ºC, flow rate of 1.0 mL/min, and detection at 215 nm. IR, NMR and LC-MS-MS were used to identify degradation product (DP2) as 3,8-dihydroxy-tetrahydro-bisthiazolo[3,4,4a,3′,4′- d]pyrazine-5,10-dione.

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&NA;. "Pidotimod." Reactions Weekly &NA;, no. 1224 (October 2008): 23. http://dx.doi.org/10.2165/00128415-200812240-00067.

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3

Baghel, Madhuri, Sangeeta Patil, Mukesh Sharma, Hemant R. Badwaik, Ruchi Khare Shrivastava, Kushagra Nagori, and Sadhana Rajput. "Degradation Kinetic Study and Mechanistic Interpretation of Hydrolysis of Pidotimod by LC-MS/MS: A QbD Assisted Stability Indicating Method Development." Asian Journal of Chemistry 34, no. 11 (2022): 2797–805. http://dx.doi.org/10.14233/ajchem.2022.23796.

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The stability of pidotimod was investigated in this study under ICH-recommended stress degradation conditions. To explore the degradation kinetics of pidotimod, a QbD assisted stability indicating assay method was designed and validated according to ICH Q2 (R1) guidelines. The impacts of hydrogen and hydroxide ions were explored, with a focus on the kinetics of pidotimod hydrolytic degradation to identify the rate laws, which were parameterized using linear regression analysis. The degradation product (DP2) was formed as a major degradation product of hydrolysis. Four known and one unknown degradation product were formed under hydrolysis. Degradation of pidotimod in acid and base degradation follows first-order reaction kinetics while the neutral degradation follows zero-order reaction kinetics. The observed degradation products of pidotimod under hydrolytic degradation were identified by LC-MS/MS analysis and a mechanism of hydrolysis is proposed.

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Ucciferri, Claudio, Katia Falasca, Marcella Reale, Manuela Tamburro, Antonio Auricchio, Francesca Vignale, and Jacopo Vecchiet. "Pidotimod and Immunological Activation in Individuals Infected with HIV." Current HIV Research 19, no. 3 (May 6, 2021): 260–68. http://dx.doi.org/10.2174/1570162x18666210111102046.

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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, IL1β, 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. Conclusions: 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.

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Riboldi, P., M. Gerosa, and P. L. Meroni. "Pidotimod: A Reappraisal." International Journal of Immunopathology and Pharmacology 22, no. 2 (April 2009): 255–62. http://dx.doi.org/10.1177/039463200902200201.

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6

Acharya, T. C., Kundan Nivangune, Snehal Muchhala, and Rishi Jain. "Effectiveness and safety of pidotimod in recurrent respiratory infections in children: a pilot study." International Journal of Contemporary Pediatrics 6, no. 5 (August 23, 2019): 2012. http://dx.doi.org/10.18203/2349-3291.ijcp20193715.

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Background: Recurrent respiratory infections (RRIs) are common in children especially in age 1 to 6 years. Pidotimod, an immunostimulant has been found to lower the recurrences of RRIs and improve the quality of life. The Objective of this study was to assess the efficacy and safety of pidotimod in children with recurrent respiratory infections (RRIs).Methods: In this single-centre, prospective, observational study, children aged 2 to 15 years diagnosed with RRIs were included. RRIs were defined as occurrence of 3 or more episodes of acute respiratory infections (ARIs) or more than 15 days of respiratory symptoms in the past 3 months. These children were treated with pidotimod in addition to standard care treatment. Treatment duration was two months and the follow-up continued for three months. Number of RRIs and severity of RRIs, antibiotic courses and rate of hospitalization before and after treatment were compared.Results: In total 25 children included in the study, mean age was 7.34±3.63 years. Among them, 68% were males. After treatment with pidotimod, there was significant reduction in mean number of ARI episodes (3.84±0.85 at baseline to 0.48±0.51 at follow-up, p<0.0001). Also, there was significant reduction in the duration of acute infectious episodes (p<0.0001), need of antibiotic courses (p<0.0001) and rates of hospitalization (p<0.0001). No safety concerns were identified and pidotimod was well tolerated.Conclusions: Addition of pidotimod to the standard treatment in children with RRIs significantly reduces the recurrence, duration of repeat infectious episodes, need of antibiotic treatments and future rates of hospitalizations. These findings support previous data.

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Ucciferri, Claudio, Alessandro Di Gasbarro, Paola Borrelli, Marta Di Nicola, Jacopo Vecchiet, and Katia Falasca. "New Therapeutic Options in Mild Moderate COVID-19 Outpatients." Microorganisms 10, no. 11 (October 27, 2022): 2131. http://dx.doi.org/10.3390/microorganisms10112131.

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Background: In recent years, the therapeutic options for COVID have significantly improved; however, the therapies are expensive with restricted access to drugs, and expeditious and difficult to manage at home. We investigated the effect of pidotimod in preventing hospitalization in patients with mild-moderate COVID-19. Methods: A total of 1231 patients between January and June 2021 were screened. A total of 184 patients with mild-moderate COVID-19 were enrolled and divided into two groups: group-A (97) had undergone therapy with pidotimod 800 mg bid for 7–10 days and group-B (87) had other therapies. We excluded those who had undergone complete vaccination course, monoclonal anti-spike/antivirals or the co-administration of pidotimod-steroid. The primary outcome chosen was the emergency room, hospitalization, and deaths for COVID-related causes; the secondary outcome chosen was the duration of COVID-19 illness. Results: A total of 34 patients (18.5%) required hospital treatment, 11 in group-A and 23 in group-B (11.3% vs. 26.4%, p = 0.008). The median disease duration in group-A was 21 days (IQR 17–27) vs. 23 (IQR 20–31) in group-B (p = 0.005). Patients in the pidotimod group had higher SpO2 in the walking test (IQR 96–99% vs. IQR 93–98%, p = 0.01) and a lower need for steroid rescue therapy (11.5% vs. 60.9%, p < 0.001). Conclusions: In the first phase of disease, pidotimod can represent an effective, low-cost, weapon, without restrictions of use, that is able to prevent a second aggressive phase and promote faster virological recovery.

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Miranda Ojeda, Rául, Raúl Enrique Ávila Yáñez, Dulce Lucero Uriostegui Cordero, Jazmín Meneses Figueroa, Antonio Pascacio Monriel, Jesús Del Moral, and Álvaro Contreras. "Pidotimod for Covid-19." Medicina e Investigación Universidad Autónoma del Estado de México 10, no. 1 (June 17, 2022): 77. http://dx.doi.org/10.36677/medicinainvestigacion.v10i1.18779.

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Covid-19 was the third leading cause of death in all of 2020, but in December 2020 and the beginning of 2021, the disease suddenly spiked and briefly became the number one cause of death in the United States (u.s.), particularly among those aged 35 years or older even though as of June 30, 2021, about 66% of adults in the u.s. have received at least one Covid-19 vaccine dose. At present, there is no drug to treat Covid-19 that can reduce the morbidity and mortality significantly, which has brought great panic to the society and scientific community. Antiviral agents and immune-modulating treatments are currently being trialed. Searches were conducted in PubMed, ScienceDirect, Google Academic, LitCovid, and MedRxiv for studies published from the beginning of 2000 through April 2021 that tested the clinical uses of pidotimod. Articles were selected prioritizing randomized clinical trials, systematic reviews, and clinical practice guidelines. Research results showed that Immunotherapy proved to be an effective method for fighting against similar viral infections to Covid-19 such as sars-cov, and Middle East respiratory syndrome coronavirus (mers-cov). studies aimed to dilucidated the mechanism of action of pidotimod, as well as randomized clinical trials that evaluate the security and utility of the drug are needed. In this scenario, the administration of Pidotimod could represent a potentially innovative strategy. In conclusion, in patients with Covid-19 without pneumonia, pidotimod could be considered an option, well-tolerated, and associated with a rapid reduction of systemic symptoms of the disease

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Ucciferri, Claudio, Antonio Auricchio, Jacopo Vecchiet, and Katia Falasca. "Improving BNT162b2 mRNA vaccine tolerability without efficacy loss by Pidotimod supplementation." Mediterranean Journal of Hematology and Infectious Diseases 14, no. 1 (February 27, 2022): e2022023. http://dx.doi.org/10.4084/mjhid.2022.023.

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Background and objectives: A new pandemic has emerged across the world:Covid-19. Covid-19 has affected hundreds of millions of people globally. To stop the spread of the virus and gain a mass immunity several vaccines have been developed. BNT162b2-mRNA-vaccine has been shown to be largely effective and is widely administered. However the vaccine is not free from adverse events that could discourage vaccination in many people. The aim was evaluated adverse effect and immunological effect after second dose of BNT162b2-mRNA-vaccine in a healthcare population that take Pidotimod versus control subjects. Methods: All nurses and doctors working in Covid-19 unit were proposed to participate, up to the enrollment of 30participants. 10 participants took Pidotimod 800mg bid orally fasting, from the fourth day before the second dose of the BNT162b2-mRNA-vaccine, for a total of six days. The remaining 20 participants did not take any therapy. We studied the differences in anti-SARS-CoV2 IgM and IgG levels and the difference of frequency of adverse events between the two groups Results: Although there was no significant difference in IgG production between the two groups, we found a lower frequency of vaccine adverse events in the group supplemented with pidotimod. Conclusions: This work demonstrates how pidotimod, despite not having a proven efficacy in increasing the production of antibodies, significantly reduces the adverse events described compared to people vaccinated without pidotimod supplementation. The results we described in this paper could encourage many more clinicians and people to vaccinate and gain the mass immunity needed to end this pandemic.

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&NA;. "Pidotimod enters its first market." Inpharma Weekly &NA;, no. 879 (March 1993): 23. http://dx.doi.org/10.2165/00128413-199308790-00062.

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11

Mailland, F., G. Signorelli, and G. Coppi. "Pidotimod < Rec INN >." Drugs of the Future 16, no. 12 (1991): 1096. http://dx.doi.org/10.1358/dof.1991.016.12.158317.

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12

&NA;. "Pidotimod a new and useful immunomodulator." Inpharma Weekly &NA;, no. 849 (August 1992): 11. http://dx.doi.org/10.2165/00128413-199208490-00021.

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13

Nagaraju K, Karthik N, Porchelvan S, Rishi Jain, and Snehal Muchhala. "An open labelled prospective clinical study to evaluate the efficacy, safety and cost analysis of Pidotimod as add-on drug for maintenance therapy in Paediatric Recurrent Acute Respiratory tract Infections." International Journal of Research in Pharmaceutical Sciences 11, no. 2 (April 27, 2020): 2183–88. http://dx.doi.org/10.26452/ijrps.v11i2.2167.

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Recurrent acute respiratory tract infections (ARTI) are the commonest form of infections affecting children irrespective of socioeconomic status and geographical limits. Immaturity of immune response involving neutrophils, NK cells, T and B cells, in the early childhood, is often cited as a reason for this RRTI. There is a comparatively high incidence of ARTI in South East Asian countries when compared with global statistics. The possibility of using immune stimulation as a method of reducing the recurrence of ARTI prompted the use of Pidotimod as an add on drug. We tried to explore the safety, efficacy and a cost benefit analysis of Pidotimod as add-on treatment for paediatric use. After registering for Clinical trial and getting IEC approval, we started an open labelled prospective single arm interventional study by recruiting 65 children between 2-12 years with ARTI to receive 800 mg daily for 15 days and 400 mg for 45 days and was followed up for 6 months. Study revealed a significant reduction in number and duration of RRTI as well as reduction in episodes requiring antibiotics and reduction in duration of treatment. The reduction in number of school days lost and treatment expenses were statistically significant. There was a significant increase in mean absolute count in CD45, CD3, CD4, CD8 and lymphocyte counts at 6 months follow-up. Hence, we conclude that 60day Pidotimod therapy has immunostimulatory activity preventing the RRTI in paediatric population when considered as an add-on therapy to standard treatment.

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Zhou, Yuanhao, Xiaolin Ye, Baikui Wang, Jiafu Ying, Zihan Zeng, Li Tang, Qi Wang, Peng Zou, Xiaoli Zhan, and Luoqin Fu. "Protective Effects of Pidotimod Against Salmonella Infections." International Journal of Peptide Research and Therapeutics 27, no. 3 (April 8, 2021): 1605–13. http://dx.doi.org/10.1007/s10989-021-10186-z.

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Ding, Li, Kaiming Luo, Carl G. Feng, and Stefan H. Oehlers. "Pidotimod increases inflammation in wounded zebrafish embryos." Fish & Shellfish Immunology 120 (January 2022): 429–33. http://dx.doi.org/10.1016/j.fsi.2021.12.013.

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Ucciferri, Claudio, Barone Mirko, Jacopo Vecchiet, and Katia Falasca. "Pidotimod in paucisymptomatic SARS-CoV2 infected patients." Mediterranean Journal of Hematology and Infectious Diseases 12, no. 1 (June 28, 2020): e2020048. http://dx.doi.org/10.4084/mjhid.2020.048.

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Mahashur, Ashok, PK Thomas, Parthiv Mehta, Kundan Nivangune, Snehal Muchhala, and Rishi Jain. "Pidotimod: In-depth review of current evidence." Lung India 36, no. 5 (2019): 422. http://dx.doi.org/10.4103/lungindia.lungindia_39_19.

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Guerra, B., A. Perino, F. Polatti, and M. Scala. "Pidotimod in the Management of Vulvar Papillomatosis." American Journal of Therapeutics 5, no. 3 (May 1998): 147–52. http://dx.doi.org/10.1097/00045391-199805000-00004.

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Pugliese, A., L. Marinelli, B. Forno, A. M. Pollono, C. Uslenghi, and R. Girardello. "Ex vivo evaluation of pidotimod effect on immune response." Pharmacological Research 26 (September 1992): 178–79. http://dx.doi.org/10.1016/1043-6618(92)90653-s.

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Huo, Xing-Xing, Lin Wang, Zhao-Wu Chen, He Chen, Xiu-Cai Xu, Ai-Mei Zhang, Xiao-Rong Song, et al. "Preventive effect of pidotimod on reactivated toxoplasmosis in mice." Parasitology Research 112, no. 8 (June 18, 2013): 3041–51. http://dx.doi.org/10.1007/s00436-013-3488-y.

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Kaczynska, Agnieszka, Martyna Kłosińska, Magdalena Ostojska, Emilia Nowak, and Paweł Stanicki. "The role of immunomodulatory preparations in asthma treatment." Journal of Education, Health and Sport 11, no. 8 (August 22, 2021): 300–306. http://dx.doi.org/10.12775/jehs.2021.11.08.032.

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Asthma remains one of the most prevalent respiratory tract disorders. The disease affects both adults and children and remains the most common cause of respiratory morbidity. Considering its significant impact on patients’ quality of life and the treatment burdened with side effects, a new therapy approaches affecting the clinical course of asthma are needed. Here we describe the current results that have been obtained on using immunomodulatory preparations in asthma. The analysis of previously published studies was conducted by using the PubMed and Scopus databases. Probiotics, bacterial lysates (BLs) and pidotimod are immunomodulatory compounds affecting both adaptive and innate immunity. The therapy based on probiotics might modulate the intestinal microbiota and regulate the inflammatory response. Bacterial lysates promote immune response by reversing Th1/Th2 unstable balance, which leads to reduction of allergen-induced airway hyperresponsiveness during asthma exacerbations. Pidotimod stimulates PRRs and increases the release of antimicrobial peptides which also leads to the improvement in the rate of respiratory tract infections. Some studies showed the beneficial effect of described preparations in asthma course. Regrettably, findings do not correspond with each other and the data referring to immunomodulatory compounds is still limited, thus there is an urgent need to conduct more, large sample studies.The conclusion we can only draw is that immunomodulatory compounds may offer an alternative approach for symptom reduction and prophylaxis against both infections and exacerbations of asthma.

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Kalyuzhin, O. V., L. O. Ponezheva, A. N. Turapova, A. Yu Nurtazina, A. S. Bykov, and A. V. Karaulov. "Interferons alpha and gamma, pidotimod, and tilorone in the treatment of acute respiratory infections in patients with allergic rhinitis: a prospective, cohort clinical and immunological study." Bulletin of Siberian Medicine 21, no. 2 (July 16, 2022): 48–59. http://dx.doi.org/10.20538/1682-0363-2022-2-48-59.

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Aim. To compare the clinical efficacy and influence on interferon (IFN) production / sensing of drugs with immunemediated antiviral effects, which potentiate type 1 (T1) immune responses, in the treatment of acute respiratory infections (ARI) in patients with allergic rhinitis.Materials and methods. 146 ARI patients with remission of seasonal allergic rhinitis were divided into 4 cohorts. In addition to symptomatic therapy, patients received either 2,000 IU of IFNγ in each nasal passage 5 times a day; or rectal suppositories containing 106 IU of IFN-α2b and antioxidants (AO) twice a day, and a gel with IFN-α2b and AO intranasally 3 times a day; or 400 mg of pidotimod per os twice a day; or 125 mg of tilorone per os on days 1, 2, 4, and 6. The severity of ARI was determined daily as the sum of 10-point scores for 15 symptoms. Serum concentrations of IFNα and IFNγ and the ability of blood cells to produce these cytokines ex vivo spontaneously and upon stimulation with Newcastle disease virus or phytohemagglutinin were studied using enzyme-linked immunosorbent assay (ELISA). The proportions of circulating lymphocytes expressing type I IFN receptor subunit 2 (CD118) or IFNγ receptor α-chain (CD119) were determined by flow cytometry.Results. ARI symptoms in all cohorts generally regressed in a similar way. However, from day 5 of the treatment, pidotimod relieved symptoms more effectively than other drugs. In patients treated with tilorone, the regression of ARI manifestations was delayed in the first two to three days, followed by rapid symptom reduction. An initial decrease in the induced production of IFNγ was found in patients treated with pidotimod, and a tendency to a decrease in this parameter was noted in other cohorts. The induced production of IFNγ after the treatment in all groups did not differ from that in healthy donors. No significant changes and differences in the proportions of CD118+ and CD119+ lymphocytes were found between the cohorts, except for a decrease in the number of CD118+ cells after the treatment with tilorone. In patients treated with IFN-α2b + AO, the proportions of CD119+ and CD118+ lymphocytes tended to increase slightly.Conclusion. Drugs that promote the development of T1 over T2 immune responses are a useful option for treating ARI in patients with allergic rhinitis.

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Manti, Sara, Giuseppe Fabio Parisi, Maria Papale, Federico Mollica, Andrea Giugno, and Salvatore Leonardi. "Efficacy and Safety of Pidotimod in Childhood Wheezing: A Pilot Study." Current Respiratory Medicine Reviews 17, no. 4 (November 2021): 226–31. http://dx.doi.org/10.2174/1573398x17666211118093930.

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Background: There is a growing need for effective therapies for the management of wheezing in the pediatric population. Aim: We conducted a pilot, mono-centre, prospective, follow-up study to assess the efficacy and the safety of Pidotimod (PDT) in the treatment of wheezing in children. Methods: Globally, 90 children (M:F=58:62, mean age 4.7±1.64 years) with recurrent viral wheezing were enrolled in the study between October-November 2018. At baseline, children received treatment with PDT as 1 vial of 400mg daily for 3 consecutive months. We evaluated the therapeutic efficacy of PDT treatment at the end of 3 (T3) months of therapy as well as the long efficacy and preventive efficacy of PDT treatment during a 3-months follow-up (T6) by using the following outcomes: (i) How many patients showed one or more episodes of viral wheezing? (ii) How many patients were taking concomitant medications (ICS, SABA, antibiotics)? (iii) How many patients required ED visits? (iv) How many patients required hospitalization? Results: A significant decrease in the number of patients with at least one or more episodes of wheezing and taking antibiotics was recorded after 3 months of treatment, and a further significant decrease for both outcomes was reported at 3-months follow-up period (p<0.05). Differently, after 3 months of treatment, we found a significant decrease in the number of patients taking ICS and SABA and in the number of patients requiring ED visits and/or hospitalization (p<0.05); however, for all these outcomes, no further significant decrease was reported at follow-up period. Conclusion: We first showed that the administration of PDT is useful in the management of patients with recurrent viral wheezing because we found a reduction in the number of patients requiring ED visits and/or hospitalization as well as the number of patients taking drugs during the treatment period. Moreover, to date, we found a long-term clinical effect over three months after treatment suspension counteracting the recurrence of the disease.

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Ruleva, A. A., S. M. Kharit, E. P. Nacharova, and I. V. Fridman. "EFFICIENCY AND SAFETY OF USING PIDOTIMOD IN VACCINATED RISK GROUP CHILDREN." Pediatric pharmacology 10, no. 1 (February 13, 2013): 70. http://dx.doi.org/10.15690/pf.v10i1.591.

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Migliorati, Graziella, Luciano D'adamio, Germano Coppi, Ildo Nicoletti, and Carlo Riccardi. "Pidotimod Stimulates Natural Killer Cell Activity and Inhibits Thymocyte Cell Death." Immunopharmacology and Immunotoxicology 14, no. 4 (January 1992): 737–48. http://dx.doi.org/10.3109/08923979209009231.

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Hu, Shenglan, Xudong Fu, Aikun Fu, Wei Du, Jian Ji, and Weifen Li. "The regulatory peptide pidotimod facilitates M2 macrophage polarization and its function." Amino Acids 46, no. 5 (January 31, 2014): 1177–85. http://dx.doi.org/10.1007/s00726-014-1676-4.

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Chen, H. S., M. Shen, and L. Y. Chen. "HILIC-MS-MS for the Quantification of Pidotimod in Human Plasma." Chromatographia 73, no. 7-8 (February 26, 2011): 767–73. http://dx.doi.org/10.1007/s10337-011-1930-9.

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Marquez-Manriquez, Juan P., PEDRO-ALEJANDRO LUCERO-DIAZ, LORENA MONTIJO-FERNANDEZ, JOSE-ANTONIO MATUTE-BRISENO, GEOBANNI TORRES MONTANO, MARK L. VERBURG, Martin-Orlando Rosas-Delgado, and ALEJANDRO CAMACHO-HERNANDEZ. "Immune effects of combinatorial repurposing drugs in refractory ovarian and colorectal cancer patients." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 122.7. http://dx.doi.org/10.4049/jimmunol.200.supp.122.7.

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Abstract Background Some refractory cancer patients have a good Karnofsky despite refractory disease. We studied the potential immunomodulatory properties of approved drugs. We used fresh PBMC from refractory patients to study the immune effects of several drugs such as metformin, pidotimod, erdostein, esomeprazole, colchicine, bortezomib, gemcitabine, zoledronic acid and naproxen. Methods 25 high-grade serous ovarian cancer (HGSOC) and 25 colorectal cancer (CRC) subjects were included after approved protocol. The inclusion criteria include Karnofsky 80–100%, complete CT scan, acute phase proteins, granzyme B ELISPOT and antigen-specific ELISA. Results We found after 24 months of treatment in HGSOC 80% of complete response (CR), 15% of stable disease (SD) and 5 % of pseudo-progressive disease (PPD). In CRC we had 50% of CR, 30% of SD and 20% of PPD. In the patients with CR there was an immunological correlation of CD8 persistent immune response by granzyme B ELISPOT in HGSOC and CRC (p=0.0001) and PR (p=0.001), respectively. The combination was well tolerated and after 10 months of stopping the treatment some patients have persistent CD8 specific immune response by ELISPOT and ELISA. Discussion The combination of daily oral metformin, colchicine, pidotimod, erdostein, and naproxen plus weekly low dose of intravenous (IV) esomeprazole (80 mg), bortezomib (0.5 mg/m2), gemcitabine (0.5 mg/m2) and zoledronic acid (100 mg) is clinically feasible, with limited clinical toxicity. We now understand the importance of preserving the CD8 immune response and the use of immune biomarkers such as antigen specific ELISA to improve the rational and generate new combinations to improve clinical outcomes in patients with refractory HGSOC and CRC.

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Ganapathy, Sridhar, Rakesh Bhatia, Kundan Nivangune, Snehal Muchhala, and Rishi Jain. "REVIEW ON THE ROLE OF PIDOTIMOD IN RECURRENT RESPIRATORY INFECTIONS IN CHILDREN." Indian Journal of Child Health 06, no. 12 (December 25, 2019): 643–49. http://dx.doi.org/10.32677/ijch.2019.v06.i12.002.

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Fu, Luo-Qin, Ya-Li Li, Ai-Kun Fu, Yan-Ping Wu, Yuan-Yuan Wang, Sheng-Lan Hu, and Wei-Fen Li. "Pidotimod exacerbates allergic pulmonary infection in an OVA mouse model of asthma." Molecular Medicine Reports 16, no. 4 (July 21, 2017): 4151–58. http://dx.doi.org/10.3892/mmr.2017.7046.

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Huang, Ji-Han, Xiao-Hui Huang, Kun Wang, Jian-Chun Li, Xue-Feng Xie, Chen-Lin Shen, Lu-Jin Li, and Qing-Shan Zheng. "Bioequivalence evaluation of two formulations of pidotimod using a limited sampling strategy." Biomedicine & Pharmacotherapy 67, no. 6 (July 2013): 475–80. http://dx.doi.org/10.1016/j.biopha.2013.03.009.

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Kalyuzhin, O. V. "The trained immunity phenomenon and mechanisms of action of non-specific immunomodifiers." Russian Journal of Allergy 12, no. 4 (December 15, 2015): 45–51. http://dx.doi.org/10.36691/rja444.

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The discovery of the trained immunity phenomenon, which explains adaptive characteristics of the components of the innate immunity, not only to modernizes our understanding of the fundamentals of anti-infectious defense, but also contributes to further progress in the development and more rational selection and use of immunomodulatory agents. Induction of memory within the innate immune response is the basis of long-lasting immunomodulating effects of some non-specific immunomodifiers, which either contain ligands for innate immunity receptors or modulate the immune response pathway mediated by these receptors. For the first time, the mechanisms of action of pidotimod (a synthetic dipeptide with immunomodulatory properties) have been re-examined in the light of the trained immunity phenomenon.

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Renzo, M. Di, A. L. Pasqui, F. Bruni, M. Saletti, G. Bova, C. Chiarion, R. Girardello, P. Ferri, and A. Auteri. "The in vitro Effect of Pidotimod on Some Immune Functions in Cancer Patients." Immunopharmacology and Immunotoxicology 19, no. 1 (January 1997): 37–51. http://dx.doi.org/10.3109/08923979709038532.

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Migliorati, G., G. Coppi, F. D'Adamio, C. Pagliacci, I. Nicoletti, and C. Riccardi. "Immunopharmacology of pidotimod: Effect on natural killer cell activity and thymocyte cell death." Pharmacological Research 26 (September 1992): 154–55. http://dx.doi.org/10.1016/1043-6618(92)90642-o.

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Capsoni, F., F. Minonzio, A. M. Ongari, R. Girardello, and C. Zanussi. "Evaluation of the kinetics of the immunomodulating activity of pidotimod on human neutrophils." Pharmacological Research 26 (September 1992): 172–73. http://dx.doi.org/10.1016/1043-6618(92)90650-z.

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Gaiduk, I. M., O. V. Turusova, D. S. Korostovtsev, N. L. Shaporova, and D. V. Breykin. "APPLICATION OF PIDOTIMOD FOR OFTEN RESPIRATORY INFECTIONS PROPHYLAXIS IN CHILDREN WITH ALLERGIC RESPIRATORY DISEASES." Current pediatrics 11, no. 5 (September 19, 2012): 156. http://dx.doi.org/10.15690/vsp.v11i5.446.

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Trabattoni, D., M. Clerici, S. Centanni, M. Mantero, M. Garziano, and F. Blasi. "Immunomodulatory effects of pidotimod in adults with community-acquired pneumonia undergoing standard antibiotic therapy." Pulmonary Pharmacology & Therapeutics 44 (June 2017): 24–29. http://dx.doi.org/10.1016/j.pupt.2017.03.005.

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38

Qu, Shaoqi, Cunchun Dai, Mei Qiu, Ruili Zhang, Chunyuan Wang, Liangliang Cui, and Zhihui Hao. "Effects of pidotimod soluble powder and immune enhancement of Newcastle disease vaccine in chickens." Immunology Letters 187 (July 2017): 14–18. http://dx.doi.org/10.1016/j.imlet.2017.05.001.

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39

Zhao, Ning, Chuanhe Liu, Chunmei Zhu, Xiaoyan Dong, and Xiuyun Liu. "Pidotimod: a review of its pharmacological features and clinical effectiveness in respiratory tract infections." Expert Review of Anti-infective Therapy 17, no. 10 (October 3, 2019): 803–18. http://dx.doi.org/10.1080/14787210.2019.1679118.

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Dou, Xiaorui, Xin Su, Yue Wang, Yadong Chen, and Weiyang Shen. "Studies on Pidotimod Enantiomers With Chiralpak-IA: Crystal Structure, Thermodynamic Parameters and Molecular Docking." Chirality 27, no. 11 (September 4, 2015): 802–8. http://dx.doi.org/10.1002/chir.22493.

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SANTANBROGIO. "Pidotimod activity on TNF-? and IL-2 gene expression in old rats infected with." Pharmacological Research 26 (September 1992): 290. http://dx.doi.org/10.1016/1043-6618(92)91288-r.

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Du, Xiao Fei, Cheng Zhe Jiang, Chun Fu Wu, Eun Kyung Won, and Se Young Choung. "Synergistic immunostimulating activity of pidotimod and red ginseng acidic polysaccharide against cyclophosphamide-induced immunosuppression." Archives of Pharmacal Research 31, no. 9 (September 2008): 1153–59. http://dx.doi.org/10.1007/s12272-001-1282-6.

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Chatterjee, Amar Nath, and Fahad Al Basir. "A Model for SARS-CoV-2 Infection with Treatment." Computational and Mathematical Methods in Medicine 2020 (September 1, 2020): 1–11. http://dx.doi.org/10.1155/2020/1352982.

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The current emergence of coronavirus (SARS-CoV-2) puts the world in threat. The structural research on the receptor recognition by SARS-CoV-2 has identified the key interactions between SARS-CoV-2 spike protein and its host (epithelial cell) receptor, also known as angiotensin-converting enzyme 2 (ACE2). It controls both the cross-species and human-to-human transmissions of SARS-CoV-2. In view of this, we propose and analyze a mathematical model for investigating the effect of CTL responses over the viral mutation to control the viral infection when a postinfection immunostimulant drug (pidotimod) is administered at regular intervals. Dynamics of the system with and without impulses have been analyzed using the basic reproduction number. This study shows that the proper dosing interval and drug dose both are important to eradicate the viral infection.

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Zeng, Z., L. Tang, Y. Zhou, B. Wang, Q. Wang, P. Zou, X. Zhan, L. Fu, and W. Li. "Effect of pidotimod on growth performance, immune function, intestinal epithelial barriers and microbiota of piglets." Journal of Animal and Feed Sciences 30, no. 1 (March 15, 2021): 64–75. http://dx.doi.org/10.22358/jafs/134117/2021.

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45

Deglurkar, Revati, Joseph L. Mathew, and Meenu Singh. "Efficacy and Safety of Pidotimod in Persistent Asthma: A Randomized Triple-Blinded Placebo-Controlled Trial." Indian Pediatrics 59, no. 3 (January 9, 2022): 201–5. http://dx.doi.org/10.1007/s13312-022-2465-x.

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Marco, Roberto Di, Francesca Condorelli, Roberto Girardello, Carla Uslenghi, Giuseppe Chisari, Maurizio Di Mauro, Anna Maria Speciale, Pier Luigi Meroni, and Ferdinando Nicoletti. "Increased Rate of Survival in Streptococcus pneumoniae-Infected Rats Treated with the New Immunomodulator Pidotimod." Scandinavian Journal of Infectious Diseases 24, no. 6 (January 1992): 821–23. http://dx.doi.org/10.3109/00365549209062473.

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Li, Ya-Li, Ai-Kun Fu, Hong-Liang Chen, Wei-Fen Li, and Luo-Qin Fu. "Potentiating effect of pidotimod on immune responses of chickens to live attenuated Newcastle disease vaccines." Italian Journal of Animal Science 15, no. 3 (July 2, 2016): 536–44. http://dx.doi.org/10.1080/1828051x.2016.1218305.

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48

Alagona, Giuliano, Caterina Ghio, and Vincenzo Villani. "Basis Set, Level, and Continuum Solvation Effects on the Stability of a Synthetic Dipeptide: PIDOTIMOD." Journal of Physical Chemistry A 103, no. 29 (July 1999): 5823–32. http://dx.doi.org/10.1021/jp991063a.

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Villani, Vincenzo, Rachele Pucciariello, Tiziano Crimella, and Riccardo Stradi. "PIDOTIMOD, a new immunostimulating dipeptide, studied by molecular mechanics, normal mode analysis and dynamics calculations." Journal of Molecular Structure 298 (October 1993): 177–90. http://dx.doi.org/10.1016/0022-2860(93)80219-l.

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Caccuri, Francesca, Antonella Bugatti, Silvia Corbellini, Sara Roversi, Alberto Zani, Pietro Mazzuca, Stefania Marsico, Arnaldo Caruso, and Cinzia Giagulli. "The Synthetic Dipeptide Pidotimod Shows a Chemokine-Like Activity through CXC Chemokine Receptor 3 (CXCR3)." International Journal of Molecular Sciences 20, no. 21 (October 24, 2019): 5287. http://dx.doi.org/10.3390/ijms20215287.

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In recent years immunomodulators have gained a strong interest and represent nowadays an active expanding area of research for the control of microbial diseases and for their therapeutic potential in preventing, treating and reducing the morbidity and mortality of different diseases. Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4carboxylic acid, PDT) is a synthetic dipeptide, which possesses immunomodulatory properties and exerts a well-defined pharmacological activity against infections, but its real mechanism of action is still undefined. Here, we show that PDT is capable of activating tyrosine phosphorylation-based cell signaling in human primary monocytes and triggering rapid adhesion and chemotaxis. PDT-induced monocyte migration requires the activation of the PI3K/Akt signaling pathway and chemokine receptor CXCR3. Indeed, a mAb to CXCR3 and a specific receptor inhibitor suppressed significantly PDT-dependent chemotaxis, and CXCR3-silenced primary monocytes lost responsiveness to PDT chemoattraction. Moreover, our results highlighted that the PDT-induced migratory activity is sustained by the CXCR3A isoform, since CXCR3-transfected L1.2 cells acquired responsiveness to PDT stimulation. Finally, we show that PDT, as CXCR3 ligands, is also able to direct the migration of IL-2 activated T cells, which express the highest levels of CXCR3 among CXCR3-expressing cells. In conclusion, our study defines a chemokine-like activity for PDT through CXCR3A and points on the possible role that this synthetic dipeptide may play in leukocyte trafficking and function. Since recent studies have highlighted diverse therapeutic roles for molecules which activates CXCR3, our findings call for an exploration of using this dipeptide in different pathological processes.

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