scholarly journals Transplant Tolerance: New Insights and Strategies for Long-Term Allograft Acceptance

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Paulina Ruiz ◽  
Paula Maldonado ◽  
Yessia Hidalgo ◽  
Alejandra Gleisner ◽  
Daniela Sauma ◽  
...  
Keyword(s):  
Organ Failure ◽  
Organ Transplantation ◽  
Therapeutic Strategy ◽  
Immunosuppressive Drugs ◽  
Past Century ◽  
The Novel ◽  
Opportunistic Pathogens ◽  
Transplant Tolerance ◽  
Disease Treatment

One of the greatest advances in medicine during the past century is the introduction of organ transplantation. This therapeutic strategy designed to treat organ failure and organ dysfunction allows to prolong the survival of many patients that are faced with no other treatment option. Today, organ transplantation between genetically dissimilar individuals (allogeneic grafting) is a procedure widely used as a therapeutic alternative in cases of organ failure, hematological disease treatment, and some malignancies. Despite the potential of organ transplantation, the administration of immunosuppressive drugs required for allograft acceptance induces severe immunosuppression in transplanted patients, which leads to serious side effects such as infection with opportunistic pathogens and the occurrence of neoplasias, in addition to the known intrinsic toxicity of these drugs. To solve this setback in allotransplantation, researchers have focused on manipulating the immune response in order to create a state of tolerance rather than unspecific immunosuppression. Here, we describe the different treatments and some of the novel immunotherapeutic strategies undertaken to induce transplantation tolerance.

scholarly journals Regulatory T Cells and Kidney Transplantation

2018 ◽  
Vol 13 (11) ◽  
pp. 1760-1764 ◽  
Author(s):  
Paloma Leticia Martin-Moreno ◽  
Sudipta Tripathi ◽  
Anil Chandraker
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Organ Transplantation ◽  
Tissue Repair ◽  
Solid Organ Transplantation ◽  
Immunosuppressive Drugs ◽  
Solid Organ ◽  
Effective Expansion ◽  
Conventional Immunosuppression

The ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4+ cells that constitutively express high levels of the IL-2 receptor α chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection. A key issue in clinical use of Tregs is how to effectively expand the number of Tregs, either through increasing numbers of endogenous Tregs or by the direct infusion of exogenously expanded Tregs. In order to realize the benefits of Treg therapy in solid organ transplantation, a number of outstanding challenges need to be overcome, including assuring an effective expansion of Tregs, improving long-term Treg stability and reduction of risk-related to off-target, nonspecific, immunosuppressive effects related specially to cancer.

scholarly journals Szervtranszplantáció gyermekkorban

2018 ◽  
Vol 159 (46) ◽  
pp. 1948-1956
Author(s):  
Antal Dezsőfi ◽  
György Reusz ◽  
Lajos Kovács ◽  
Dolóresz Szabó ◽  
Kata Kelen ◽  
...  
Keyword(s):  
Organ Failure ◽  
Organ Transplantation ◽  
Immunosuppressive Drugs ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Donor Organ ◽  
Success Story ◽  
Childhood Diseases ◽  
Before And After ◽  
Working Groups ◽  
End Stage

Abstract: Paediatric organ transplantation today is considered and accepted and widely available therapy in children with end-stage organ failure. It is important to know that in childhood, diseases leading to end-stage organ failure differ from those in adults. Beside this, in children there are different surgical and paediatric challenges before and after transplantation (size differences of the patient and donor organ, special and paediatric infections, different pharmacokinetics and pharmacodynamics of immunosuppressive drugs, noncompliance). However, paediatric organ transplantation in the last decades became a success story of the Hungarian health care owing to several working groups in Hungary and outside the country. Orv Hetil. 2018; 159(46): 1948–1956.

scholarly journals Special considerations in generic substitution of immunosuppressive drugs in transplantation

2012 ◽  
Vol 153 (34) ◽  
pp. 1341-1349
Author(s):  
Ádám Remport ◽  
Dávid Dankó ◽  
Zsuzsa Gerlei ◽  
Krisztina Czebe ◽  
István Kiss
Keyword(s):  
Organ Transplantation ◽  
Generic Substitution ◽  
Kidney Transplant Recipient ◽  
Immunosuppressive Treatment ◽  
Solid Organ Transplantation ◽  
Immunosuppressive Drugs ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Published Evidence

Long-term success in solid organ transplantation strongly depends on the optimal use of maintenance immunosuppressive treatment. Cyclosporin and tacrolimus are the most frequently administered immunosuppressants and they are designed to narrow therapeutic index drugs. The substitution of the branded formulation by their generic counterparts may lead to economic benefit only if equivalent clinical outcomes can be achieved. There is no published evidence to date on the guarantee of their long-term therapeutic equivalence and cases of therapeutic failures have been reported due to inadvertent drug conversion. The disadvantageous clinical consequences of a non medical, mechanistic forced switch from the original to generic formulation of tacrolimus and the estimated loss of the payer’s presumed savings are presented in a kidney transplant recipient population. Special problems related to pediatric patients, drug interactions with concurrent medications and the burden of additional therapeutic drug monitoring and follow up visits are also discussed. The authors are convinced that the implementation of the European Society of Organ Transplantation guidelines on generic substitution may provide a safe way for patients and healthcare payers. Orv. Hetil., 2012, 153, 1341–1349.

scholarly journals Bioengineering of the Uterus

2021 ◽  
Author(s):  
Yushi Yoshimasa ◽  
Tetsuo Maruyama
Keyword(s):  
Therapeutic Strategy ◽  
Experimental Treatment ◽  
Immunosuppressive Drugs ◽  
Perinatal Complications ◽  
Comprehensive Overview ◽  
Asherman’S Syndrome ◽  
The Past ◽  
Synthetic Materials ◽  
And Function

AbstractImpairment of uterine structure and function causes infertility, pregnancy loss, and perinatal complications in humans. Some types of uterine impairments such as Asherman’s syndrome, also known as uterine synechiae, can be treated medically and surgically in a standard clinical setting, but absolute defects of uterine function or structure cannot be cured by conventional approaches. To overcome such hurdles, partial or whole regeneration and reconstruction of the uterus have recently emerged as new therapeutic strategies. Transplantation of the whole uterus into patients with uterine agenesis results in the successful birth of children. However, it remains an experimental treatment with numerous difficulties such as the need for continuous and long-term use of immunosuppressive drugs until a live birth is achieved. Thus, the generation of the uterus by tissue engineering technologies has become an alternative but indispensable therapeutic strategy to treat patients without a functional or well-structured uterus. For the past 20 years, the bioengineering of the uterus has been studied intensively in animal models, providing the basis for clinical applications. A variety of templates and scaffolds made from natural biomaterials, synthetic materials, or decellularized matrices have been characterized to efficiently generate the uterus in a manner similar to the bioengineering of other organs and tissues. The goal of this review is to provide a comprehensive overview and perspectives of uterine bioengineering focusing on the type, preparation, and characteristics of the currently available scaffolds.

Concussion in sports in children and adolescents – to play or not to play?

2017 ◽  
Vol 65 (3) ◽  
Keyword(s):  
Gender Differences ◽  
Children And Adolescents ◽  
Return To Sport ◽  
Consensus Conference ◽  
Return To School ◽  
The Novel ◽  
International Consensus ◽  
Persistent Symptoms ◽  
New Findings

A lot has been published on the topic concussion in sports during the last years, conscience was sharpened, much was structured and defined more precisely, help tools were developed and rules changed. This article summarizes the fifth edition of the recently published guidelines of the “International Consensus Conference on Concussion in Sport”. In addition, new findings regarding gender differences and recovery will be presented, as well as the modified “return-to-sport” and the novel “return-to-school” protocols. Despite increased knowledge many questions remain such as the therapy of persistent symptoms or long-term sequelae of recurrent concussions.

scholarly journals Waning antibody responses in COVID-19: what can we learn from the analysis of other coronaviruses?

Infection ◽  
2021 ◽  
Author(s):  
Ali Hamady ◽  
JinJu Lee ◽  
Zuzanna A. Loboda
Keyword(s):  
Cross Reactivity ◽  
Antibody Responses ◽  
The Novel ◽  
Incidence And Mortality ◽  
Antibody Titres ◽  
Human Coronaviruses ◽  
Public Health Strategies ◽  
Antibody Dynamics

Abstract Objectives The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical. Methods/Results In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1–2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity. Conclusion Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.

scholarly journals Long-Term Experimental Evolution in Escherichia coli. IV. Targets of Selection and the Specificity of Adaptation

Genetics ◽  
1996 ◽  
Vol 143 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Michael Travisano ◽  
Richard E Lenski
Keyword(s):  
Escherichia Coli ◽  
Experimental Evolution ◽  
Common Ancestor ◽  
The Novel ◽  
Physiological Mechanisms ◽  
Outer Membranes ◽  
Limiting Nutrient ◽  
Novel Environments ◽  
Uptake Mechanisms

Abstract This study investigates the physiological manifestation of adaptive evolutionary change in 12 replicate populations of Escherichia coli that were propagated for 2000 generations in a glucose-limited environment. Representative genotypes from each population were assayed for fitness relative to their common ancestor in the experimental glucose environment and in 11 novel single-nutrient environments. After 2000 generations, the 12 derived genotypes had diverged into at least six distinct phenotypic classes. The nutrients were classified into four groups based upon their uptake physiology. All 12 derived genotypes improved in fitness by similar amounts in the glucose environment, and this pattern of parallel fitness gains was also seen in those novel environments where the limiting nutrient shared uptake mechanisms with glucose. Fitness showed little or no consistent improvement, but much greater genetic variation, in novel environments where the limiting nutrient differed from glucose in its uptake mechanisms. This pattern of fitness variation in the novel nutrient environments suggests that the independently derived genotypes adapted to the glucose environment by similar, but not identical, changes in the physiological mechanisms for moving glucose across both the inner and outer membranes.

scholarly journals AB0509 SUSPENSIVE EFFICACY OF TOCILIZUMAB IN TREATMENT-NAÏVE PATIENTS WITH TAKAYASU ARTERITIS: TOCITAKA FRENCH PROSPECTIVE MULTICENTER OPEN-LABELLED TRIAL.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1552.3-1552
Author(s):  
A. Mekinian ◽  
D. Saadoun ◽  
J. C. N. F. [email protected] ◽  
I. Q. M. F. [email protected] ◽  
P. Jégo ◽  
...  
Keyword(s):  
Disease Activity ◽  
Takayasu Arteritis ◽  
Immunosuppressive Drugs ◽  
Relapse Free Survival ◽  
Research Support ◽  
Free Survival ◽  
Treatment Naïve ◽  
Steroid Sparing

Objectives:To assess long term efficacy of tocilizumab in treatment-naive patients with Takayasu arteritis (TAK).Methods:In this multicenter, prospective, open-labelled trial, we aim to evaluate the benefit of adding tocilizumab to steroids in treatment-naïve patients with TAK, on discontinuation of steroids after 6 months of tocilizumab treatment, and to assess relapse-free survival following tocilizumab discontinuation.Results:Thirteen patients with TAK were included, with a median age of 32 years [19-45] and 12 (92%) females. Six (54%) patients met the primary end-point. Among 11 (85%) patients which achieved remission at 6 months, 6 (54%) have reached primary endpoint.. Among the 5 remaining patients which continued steroids, 3 had a prednisone-equivalent dosage < 5mg/day. A significant decrease of disease activity was observed after 6 months of tocilizumab therapy: decrease of median NIH scale (3 [3-4] at baseline, versus 1 [0-2] after 6 months; p <0.001), ITAS-2010 score (5 [2-7] versus 3 [0-8]; p = 0.002), and ITAS-A score (7 [4-10] versus 4 [1-15]; p = 0.0001)]. All patients discontinued tocilizumab after 7 infusions, and no other immunosuppressive drugs was introduced, except for 1 patient which received methotrexate. After 9 and 12 months, respectively 7 (54%) and 6 (50%) patients achieved remission with less than 7.5 mg/day of prednisone, and 9 (69%) and 9 (75%) with doses <10 mg/day. During the 12 months follow-up after tocilizumab discontinuation, a relapse occurred among 5 patients (45%) out of 11 in which achieved remission after 6 months of tocilizumab.No severe AEs were considered related to study treatment and none required tocilizumab interruption or dose reduction. No deaths have occurred during the study period.Conclusion:Tocilizumab seems an effective steroid sparing therapy in TAK but its effect appears to be suspensive.Disclosure of Interests:Arsene Mekinian: None declared, david Saadoun: None declared, [email protected] [email protected]: None declared, [email protected] [email protected]: None declared, Patrick Jégo: None declared, [email protected] [email protected]: None declared, wxv wxv: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Mathieu Vautier: None declared, [email protected]>; [email protected]>;: None declared, Patrice cacoub: None declared, olivier fain: None declared

scholarly journals Barley Seeds miRNome Stability during Long-Term Storage and Aging

2021 ◽  
Vol 22 (9) ◽  
pp. 4315
Author(s):  
Marta Puchta ◽  
Jolanta Groszyk ◽  
Magdalena Małecka ◽  
Marek D. Koter ◽  
Maciej Niedzielski ◽  
...  
Keyword(s):  
Seed Viability ◽  
Small Rna Sequencing ◽  
The Novel ◽  
Seed Aging ◽  
Long Term Storage ◽  
Novel Mirna ◽  
Complex Biological Process ◽  
Almost All ◽  
Term Storage

Seed aging is a complex biological process that has been attracting scientists’ attention for many years. High-throughput small RNA sequencing was applied to examine microRNAs contribution in barley seeds senescence. Unique samples of seeds that, despite having the same genetic makeup, differed in viability after over 45 years of storage in a dry state were investigated. In total, 61 known and 81 novel miRNA were identified in dry seeds. The highest level of expression was found in four conserved miRNA families, i.e., miR159, miR156, miR166, and miR168. However, the most astonishing result was the lack of significant differences in the level of almost all miRNAs in seed samples with significantly different viability. This result reveals that miRNAs in dry seeds are extremely stable. This is also the first identified RNA fraction that is not deteriorating along with the loss of seed viability. Moreover, the novel miRNA hvu-new41, with higher expression in seeds with the lowest viability as detected by RT-qPCR, has the potential to become an indicator of the decreasing viability of seeds during storage in a dry state.

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