immunosuppressive agent
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2022 ◽  
Vol 29 (1) ◽  
pp. 267-282
Author(s):  
Yi-Xiu Long ◽  
Yue Sun ◽  
Rui-Zhi Liu ◽  
Ming-Yi Zhang ◽  
Jing Zhao ◽  
...  

Purpose: Immune-related pneumonitis (IRP) has attracted extensive attention, owing to its increased mortality rate. Conventional chemotherapy (C) has been considered as an immunosuppressive agent and may thus reduce IRP’s risk when used in combination with PD-1/L1 inhibitors. This study aimed to assess the risk of IRP with PD-1/L1 inhibitors plus chemotherapy (I+C) versus PD-1/L1 inhibitors alone (I) in solid cancer treatment. Method: Multiple databases were searched for RCTs before January 2021. This NMA was performed among I+C, I, and C to investigate IRP’s risk. Subgroup analysis was carried out on the basis of different PD-1/L1 inhibitors and cancer types. Results: Thirty-one RCTs (19,624 patients) were included. The I+C group exhibited a lower risk of IRP in any grade (RR, 0.60; 95% CI, 0.38–0.95) and in grade 3–5 (RR, 0.42; 95% CI, 0.21–0.92) as opposed to the I group. The risk of any grade IRP with PD-1 plus chemotherapy was lower than that with PD-1 monotherapy (RR, 0.50; 95% CI, 0.28–0.89), although grade 3–5 IRP was similar. There was no statistically meaningful difference in the risk of any grade IRP between PD-L1 plus chemotherapy and PD-L1 inhibitors monotherapy (RR, 0.95; 95% CI, 0.43–2.09) or grade 3–5 IRP (RR, 0.71;95% CI, 0.24–2.07). In addition, compared with the I group, the I+C group was correlated with a decreased risk in IRP regardless of cancer type, while a substantial difference was only observed in NSCLC patients for grade 3–5 IRP (RR, 0.39; 95% CI, 0.15–0.98). Conclusion: In comparison to PD-1/L1 inhibitor treatment alone, combining chemotherapy with PD-1/L1 inhibitors might reduce the risk of IRP in the general population. Furthermore, PD-1 inhibitors in combination with chemotherapy were correlated with a decreased risk of IRP compared to PD-1 inhibitor treatment alone. In contrast to the I group, the I+C group exhibited a lower risk of IRP, especially for NSCLC patients.


Animals ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 62
Author(s):  
Antonietta Di Francesco ◽  
Giulia Quaglia ◽  
Daniela Salvatore ◽  
Sonia Sakhria ◽  
Elena Catelli ◽  
...  

Chicken infectious anemia virus (CIAV) is an economically important and widely distributed immunosuppressive agent in chickens. This study performed an epidemiological investigation on CIAV circulation in 195 Tunisian broilers, belonging to 13 lots from five industrial farms and in one rural farm. Fifteen animals were detected positive by a VP1 nested PCR. The amplicons were molecularly characterised by complete genome sequencing. All positive samples obtained in this study were from the rural farm, whereas the industrial farms sampled were negative. Nucleotide and amino acid sequence analyses showed a high degree of similarity among the sequences obtained, suggesting the circulation of a single CIAV strain in the positive lot. Phylogenetic analysis based on the CIAV VP1 nucleotide sequence and/or the complete genome showed that the sequences obtained in this study clustered with CIAV strains previously detected in Tunisia, Italy and Egypt, belonging to genogroup II. Our results highlight the need for constant CIAV surveillance in backyard chicken production.


2021 ◽  
Vol 20 (4) ◽  
pp. 18-25
Author(s):  
E. A. Pogodina ◽  
A. V. Lobov ◽  
P. I. Ivanova ◽  
V. I. Kazey ◽  
I. Zh. Shubina

The aim of the review is studying the immune response to the new coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus in different populations, including those with immunosuppression due to concomitant diseases or immunosuppressive therapy.The role of T cells in building up the anti-COVID-19 immunity is of special interest, particularly, when comparing T cell and antibody based immunity. A number of studies are focused on the effectiveness of T-cell immunity against SARS-CoV-2 infection, as well as on the resistance to re-infection. The decreased immunity associated with such illnesses as autoimmune diseases, non-autoimmune inflammations, and the effect of immunosuppressive drugs and obviously, different cancers increase the susceptibility to SARS-CoV-2 and COVID-19 development, and exacerbate the course of the disease.Several studies showed that patients with cancer are at risk of impaired immune response associated with a malignant neoplasm. The inefficient immune response was also shown in cancer patients receiving immunomodulatory therapy. However, some studies registered the specific immunogenicity after vaccination in patients with concomitant immunosuppression.Methotrexate is a folate antimetabolite. The drug can be used both in high doses as an antimetabolite in the antitumor therapy, and in low doses as an immunosuppressive agent in patients with autoimmune diseases. Therefore, the review also discusses a study that evaluated the humoral and cellular immune response to the BNT162b2 (PfizerBioNTech) anti-COVID-19 vaccine in patients receiving methotrexate. The rate of antibody production was lower in patients receiving methotrexate, though the level of T-cell response was similar in all groups studied.The review discussed immune compromised patients with cancer and hematological malignancies and patients living with HIV who had COVID-19. Most studies reported no significant differences of COVID-19 outcomes between major population and the patients with suppressed immune system.Hereby, the cell and humoral immune response in immune compromised patients is possible, however, additional studies are required to confirm these data.


2021 ◽  
Vol 15 (11) ◽  
pp. 2996-2998
Author(s):  
Mujtaba Ali Hasnain ◽  
Samrah Mujtaba ◽  
Iqra Javed ◽  
Saima Abdul Waheed ◽  
Muhammad Shahzad Gul ◽  
...  

Background: Mycophenolate, an immunosuppressive agent choice. It is used readily in the transplantation of kidneys. Aim: To find out utilization of this drug is considered safe but the exact dosage of this drug varies according to the choice. Methods: It alters from fixed-dose to the dose optimization to the drug exposure target. It is the area under the concentration and time curve graph. This graph gives inconsistent results of concentration-controlled dosing in prospective studies. In this research paper, the evidence helping mycophenolate has been analyzed. The research includes finding out the pharmacological features, toxicities, and efficacy of this chemical ingredient. Randomized controlled trials along with dose optimization procedure and exposure have also been achieved. Results: A fixed dose of mycophenolate continuously leads to either less exposure associated with unapproved strategy or over-exposure leading to toxicity. When concentration controlled dosing is measured via pharmacokinetic measurement to target concentration intervention, mycophenolate exposure is controlled successfully and clinical benefits are visible. There is a need for agreement on practical aspects of drug-target concentration intervention in normal tacrolimus containing dosage and research to find maintenance phase subjection targets. Conclusion: More preference should be given to the effects of over suppression and under suppression in transplantation of kidney affecting short term as well as long term benefits. A single dose should be given to the mycophenolate target concentration intervention. Keywords: Mycophenolate, immunosuppressive agent, kidney transplant, target dose intervention


MedPharmRes ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 27-32
Author(s):  
Thuan Thi Minh Nguyen ◽  
Minh Hue Nguyen

Methotrexate (MTX) is a chemotherapy and immunosuppressive agent widely used to treat cancer, autoimmune diseases in children and adult patients, and ectopic pregnancy. However, MTX is highly toxic to the liver, kidney, and nervous system. This study aimed to quantify the concentration of MTX in human plasma using high-performance liquid chromatography (HPLC). MTX and its internal standard (para aminoacetophenone-PAPA) in plasma samples were extracted simultaneously with methanol. Sample purity was performed using the 1 cc OASIS HLB cartridges. Sample injection volume of 10 µL was analyzed on a Lichrocart Supersil 125-4 column C18 maintained at 40 °C on a Waters 2695 XE equipped with a PDA detector set at 303 nm. The mobile phase contained phosphate buffer (pH 6.0) and methanol at a ratio of 80:20 (v/v) and was maintained at a flow rate of 1 ml/min. The results showed that the total time of chromatographic analysis was 15 min. MTX and PAAP were found in the chromatograms at retention times of 2.3 and 5.2 min, respectively. The linear range of the MTX from 0.5 to 25 µg/mL. Intra-day and inter-day imprecision for MTX ranged from 3.42 to 8.128%. LLOQ of MTX was 0.5 µg/mL and the extraction effects were above 77%. In conclusion, we developed and validated a simple HPLC method to determine the MTX concentrations in human plasma.


2021 ◽  
Vol 22 (22) ◽  
pp. 12520
Author(s):  
Manigandan Krishnan ◽  
Joonhyeok Choi ◽  
Ahjin Jang ◽  
Young Kyung Yoon ◽  
Yangmee Kim

Carbapenem-resistant A. baumannii (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effects. In this study, we attempted to produce safer peptide antibiotics against CRAB by reversing the parent sequence to generate R-Pro9-3 and R-Pro9-3D. Among the tested peptides, R-Pro9-3D had the most rapid and effective antibacterial activity against Gram-negative bacteria, particularly clinical CRAB isolates. Analyses of antimicrobial mechanisms based on lipopolysaccharide (LPS)-neutralization, LPS binding, and membrane depolarization, as well as SEM ultrastructural investigations, revealed that R-Pro9-3D binds strongly to LPS and impairs the membrane integrity of CRAB by effectively permeabilizing its outer membrane. R-Pro9-3D was also less cytotoxic and had better proteolytic stability than Pro9-3D and killed biofilm forming CRAB. As an LPS-neutralizing peptide, R-Pro9-3D effectively reduced LPS-induced pro-inflammatory cytokine levels in RAW 264.7 cells. The antiseptic abilities of R-Pro9-3D were also investigated using a mouse model of CRAB-induced sepsis, which revealed that R-Pro9-3D reduced multiple organ damage and attenuated systemic infection by acting as an antibacterial and immunosuppressive agent. Thus, R-Pro9-3D displays potential as a novel antiseptic peptide for treating Gram-negative CRAB infections.


2021 ◽  
Vol 2 (4) ◽  
pp. 441-454
Author(s):  
Islam B Mohamed ◽  
Fuad Z Aloor ◽  
Prasun K Jalal

Since the first liver transplantation operation (LT) in 1967 by Thomas Starzl, efforts to increase survival and prevent rejection have taken place. The development of calcineurin inhibitors (CNIs) in the 1980s led to a surge in survival post-transplantation, and since then, strategies to prevent graft loss and preserve long-term graft function have been prioritized. Allograft rejection is mediated by the host immune response to donor antigens. Prevention of rejection can be achieved through either immunosuppression or induction of tolerance. This leads to a clinical dilemma, as the choice of an immunosuppressive agent is not an easy task, with considerable patient and graft-related morbidities. On the other hand, the induction of graft tolerance remains a challenge. Despite the fact that the liver exhibits less rejection than any other transplanted organs, spontaneous graft tolerance is rare. Most immunosuppressive medications have been incriminated in renal, cardiovascular, and neurological complications, relapse of viral hepatitis, and recurrence of HCC and other cancers. Efforts to minimize immunosuppression are directed toward decreasing medication side effects, increasing cost effectiveness, and decreasing economic burden without increasing the risk of rejection. In this article, we will discuss recent advances in strategies for improving immunosuppression following liver transplantation.


Author(s):  
Jitendra Kishore Singh ◽  
Yogesh Rupram Zanwar ◽  
Jagannath Kumar ◽  
Jatin Jayeshbhai Patel ◽  
Vineet Chandrabhushan Dube ◽  
...  

Topical corticosteroids are the cornerstone in managing several dermatologic disorders, including plaque psoriasis.Managing plaque psoriasis warrants the use of an effective anti-inflammatory, antimitotic, antipruritic, and immunosuppressive agent, such as clobetasol propionate (CP). Recently, CP 0.025% cream received approval by United States food and drug administration (US FDA) for the treatment of moderate-to-severe psoriasis in adult patients. CP 0.025% cream has proven efficacious in chronic skin diseases, including controlling inflammation and pruritus, in various steroid-responsive dermatoses. In contrast to prior CP formulations, this novel CP 0.025% cream formulation does not contain propylene glycol, short-chain alcohols, and sorbitol-based emulsifiers, which are known contact allergens. The other beneficial attributes of this CP 0.025% cream formulation are high penetration of active ingredients and a lower degree of systemic absorption. This case series discusses the experience of using CP 0.025% cream in terms of its efficacy and safety in various dermatologic conditions. 


2021 ◽  
pp. 108324
Author(s):  
Zakiye Ganjei ◽  
Hoorvash Faraji Dana ◽  
Sepehr Ebrahimi-Dehkordi ◽  
Fereshte Alidoust ◽  
Kiumars Bahmani

2021 ◽  
Vol 15 (09) ◽  
pp. 1257-1262
Author(s):  
Satriyo Dwi Suryantoro ◽  
Mochammad Thaha ◽  
Pranawa ◽  
Djoko Santoso ◽  
Nunuk Mardiana ◽  
...  

Severe COVID-19 infection management for a recipient of kidney transplant has debatable prognosis and treatment. We described the case of a COVID-19 infected 70 year old female, previously had renal transplantation in 2017. The patient took immunosuppressive agents as routine drugs for transplant recipient status and received lopinavir/ritonavir, hydroxychloroquine, and dexamethasone daily at the hospitalization. Specific question arises about renal transplant recipients being infected by COVID-19 – whether the infection will get worse compared to those without immunosuppresive agent. In this case, author decided to stop the immunosuppressive agent followed administration of combination lopinavir/ritonavir, hydroxychloroquine, and dexamethasone that gives a good clinical impact change to patient’s condition after once getting worsened and mechanically ventilated. Nevertheless, the assessment of risk and benefit in continuing immunosuppressive drugs is concurrently essential due to the prevention of transplant rejection.


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