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Nature Jun 2021Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly. To define the contribution of immune system ageing to...
Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly. To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1, which encodes a crucial DNA repair protein, in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence in the immune system only. We show that Vav-iCre;Ercc1 mice were healthy into adulthood, then displayed premature onset of immunosenescence characterized by attrition and senescence of specific immune cell populations and impaired immune function, similar to changes that occur during ageing in wild-type mice. Notably, non-lymphoid organs also showed increased senescence and damage, which suggests that senescent, aged immune cells can promote systemic ageing. The transplantation of splenocytes from Vav-iCre;Ercc1 or aged wild-type mice into young mice induced senescence in trans, whereas the transplantation of young immune cells attenuated senescence. The treatment of Vav-iCre;Ercc1 mice with rapamycin reduced markers of senescence in immune cells and improved immune function. These data demonstrate that an aged, senescent immune system has a causal role in driving systemic ageing and therefore represents a key therapeutic target to extend healthy ageing.
Topics: Aging; Animals; DNA Damage; DNA Repair; DNA-Binding Proteins; Endonucleases; Female; Healthy Aging; Homeostasis; Immune System; Immunosenescence; Male; Mice; Organ Specificity; Rejuvenation; Sirolimus; Spleen
PubMed: 33981041
DOI: 10.1038/s41586-021-03547-7 -
Transplant International : Official... Nov 2021The future clinical application of animal-to-human transplantation (xenotransplantation) is of importance to society as a whole. Favourable preclinical data relevant to... (Review)
Review
The future clinical application of animal-to-human transplantation (xenotransplantation) is of importance to society as a whole. Favourable preclinical data relevant to cell, tissue and solid organ xenotransplants have been obtained from many animal models utilizing genetic engineering and protocols of pathogen-free husbandry. Findings have reached a tipping point, and xenotransplantation of solid organs is approaching clinical evaluation, the process of which now requires close deliberation. Such discussions include considering when there is sufficient evidence from preclinical animal studies to start first-in-human xenotransplantation trials. The present article is based on evidence and opinions formulated by members of the European Society for Organ Transplantation who are involved in the Transplantation Learning Journey project. The article includes a brief overview of preclinical concepts and biology of solid organ xenotransplantation, discusses the selection of candidates for first-in-human studies and considers requirements for study design and conduct. In addition, the paper emphasizes the need for a regulatory framework for xenotransplantation of solid organs and the essential requirement for input from public and patient stakeholders.
Topics: Animals; Heterografts; Humans; Models, Animal; Organ Transplantation; Transplantation, Heterologous; Transplants
PubMed: 34459040
DOI: 10.1111/tri.14031 -
American Family Physician Dec 2013Onychomycosis is a fungal infection of the nails that causes discoloration, thickening, and separation from the nail bed. Onychomycosis occurs in 10% of the general... (Review)
Review
Onychomycosis is a fungal infection of the nails that causes discoloration, thickening, and separation from the nail bed. Onychomycosis occurs in 10% of the general population, 20% of persons older than 60 years, and 50% of those older than 70 years. It is caused by a variety of organisms, but most cases are caused by dermatophytes. Accurate diagnosis involves physical and microscopic examination and culture. Histologic evaluation using periodic acid-Schiff staining increases sensitivity for detecting infection. Treatment is aimed at eradication of the causative organism and return to a normal appearance of the nail. Systemic antifungals are the most effective treatment, with meta-analyses showing mycotic cure rates of 76% for terbinafine, 63% for itraconazole with pulse dosing, 59% for itraconazole with continuous dosing, and 48% for fluconazole. Concomitant nail debridement further increases cure rates. Topical therapy with ciclopirox is less effective; it has a failure rate exceeding 60%. Several nonprescription treatments have also been evaluated. Laser and photodynamic therapies show promise based on in-vitro evaluation, but more clinical studies are needed. Despite treatment, the recurrence rate of onychomycosis is 10% to 50% as a result of reinfection or lack of mycotic cure.
Topics: Administration, Topical; Algorithms; Antifungal Agents; Combined Modality Therapy; Debridement; Decision Support Techniques; Humans; Lasers, Solid-State; Nonprescription Drugs; Onychomycosis; Photochemotherapy; Treatment Failure
PubMed: 24364524
DOI: No ID Found -
American Journal of Transplantation :... Feb 2023The American Society of Transplant Surgeons supports efforts to increase the number of organs that are critically needed for patients desperately awaiting... (Review)
Review
The American Society of Transplant Surgeons supports efforts to increase the number of organs that are critically needed for patients desperately awaiting transplantation. In the United States, transplantation using organs procured from donation after circulatory death (DCD) donors has continued to increase in number. Despite these increases, substantial variability in the utilization and practices of DCD transplantation still exists. To improve DCD organ utilization, it is important to create a set of best practices for DCD recovery. The following recommendations aim to provide guidance on contemporary issues surrounding DCD organ procurement in the United States. A work group was composed of members of the American Society of Transplant Surgeon Scientific Studies Committee and the Thoracic Organ Transplantation Committee. The following topics were identified by the group either as controversial or lacking standardization: prewithdrawal preparation, definition of donor warm ischemia time, DCD surgical technique, combined thoracic and abdominal procurements, and normothermic regional perfusion. The proposed recommendations were classified on the basis of the grade of available evidence and the strength of the recommendation. This information should be valuable for transplant programs as well as for organ procurement organizations and donor hospitals as they develop robust DCD donor procurement protocols.
Topics: Humans; United States; Tissue and Organ Procurement; Organ Transplantation; Tissue Donors; Cardiovascular System; Perfusion; Death; Organ Preservation
PubMed: 36695685
DOI: 10.1016/j.ajt.2022.10.009 -
Current Biology : CB Mar 2016Animal communication, including that among humans, is fascinating in its efficiency, diversity and its complexity. The evolution of a communication signal requires that...
Animal communication, including that among humans, is fascinating in its efficiency, diversity and its complexity. The evolution of a communication signal requires that the encoded content sent by an organism (sender) is detected and decoded by a receiver, who then must respond in such a way that the fitness of the sender is increased. The signal could be visual, such as bright coloration or some stereotypical movement that attracts attention through the sense of sight. It could be chemical, such as a pheromone we detect by smell or taste, or it could be tactile, involving direct physical touch. It could be an acoustic wave, detected by an auditory organ as sound and perceived through the sense of hearing, or it could be a vibrational wave detected by a vibration receiver of another sort. The medium through which the signal is transmitted could be any that exists on the Earth (solid, liquid or gas), and each type of medium influences the type of signal that is able to most efficiently move through it.
Topics: Animal Communication; Animals
PubMed: 26954435
DOI: 10.1016/j.cub.2016.01.054 -
Organogenesis 2018The transplantation of living cells, tissues or organs from one species to another is termed xenotransplantation. The history of xenotransplantation is as old as...
The transplantation of living cells, tissues or organs from one species to another is termed xenotransplantation. The history of xenotransplantation is as old as allogeneic transplantation itself. Early attempts were made at a time when the immunologic basis of organ rejection were poorly understood. The advent of potent immunosuppressive medications along with the parallel advances in the field of genetic engineering has provided a fresh perspective on the role of xenotransplantation as a means to alleviate the disparity between the number of candidates on the waitlist and the available organs. As the science behind xenotransplantation advances, the transplantation community must take it upon themselves to educate the community at large regarding both the benefits and potential risks of this promising field.
PubMed: 30252598
DOI: 10.1080/15476278.2018.1517508 -
Mechanisms of Ageing and Development Dec 2021Older organs provide a substantial unrealized potential with the capacity to close the gap between demand and supply in organ transplantation. The potential of... (Review)
Review
Older organs provide a substantial unrealized potential with the capacity to close the gap between demand and supply in organ transplantation. The potential of senolytics in improving age-related conditions has been shown in various experimental studies and early clinical trials. Those encouraging data may also be of relevance for transplantation. As age-differences between donor and recipients are not uncommon, aging may be accelerated in recipients when transplanting older organs; young organs may, at least in theory, have the potential to 'rejuvenate' old recipients. Here, we review the relevance of senescent cells and the effects of senolytics on organ quality, alloimmune responses and outcomes in solid organ transplantation. This article is part of the Special Issue - Senolytics - Edited by Joao Passos and Diana Jurk.
Topics: Aging, Premature; Cellular Senescence; Humans; Organ Transplantation; Senotherapeutics; Tissue Survival
PubMed: 34606875
DOI: 10.1016/j.mad.2021.111582 -
Transplantation Sep 2019Single-cell RNA sequencing (scRNA-seq) allows the measurement of transcriptomes from individual cells providing new insights into complex biological systems. scRNA-seq... (Review)
Review
Single-cell RNA sequencing (scRNA-seq) allows the measurement of transcriptomes from individual cells providing new insights into complex biological systems. scRNA-seq has enabled the identification of rare cell types, new cell states, and intercellular communication networks that may be masked by traditional bulk transcriptional profiling. Researchers are increasingly using scRNA-seq to comprehensively characterize complex organs in health and disease. The diversity of immune cell types, some present at low frequency, in a transplanted organ undergoing rejection makes scRNA-seq ideally suited to characterize transplant pathologies because it can quantify subtle transcriptional differences between rare cell types. In this review, we discuss single-cell sequencing methods and their application in transplantation to date, current challenges, and future directions. We believe that the remarkably rapid pace of technological development in this field makes it likely that single-cell technologies such as scRNA-seq will have an impact on clinical transplantation within a decade.
Topics: Animals; Gene Expression Regulation; Gene Regulatory Networks; Humans; Organ Transplantation; Predictive Value of Tests; RNA-Seq; Risk Factors; Signal Transduction; Single-Cell Analysis; Transcriptome; Treatment Outcome
PubMed: 30946217
DOI: 10.1097/TP.0000000000002725 -
Indian Journal of Medical Ethics 2022The gap between demand and supply of organs continues to widen worldwide, encouraging transplant commercialism. While solid organ commerce is most prevalent in...
The gap between demand and supply of organs continues to widen worldwide, encouraging transplant commercialism. While solid organ commerce is most prevalent in impoverished countries, commercialisation of body parts such as tissues is prevalent in economically developed countries. A number of international legal instruments and transplant societies define, condemn, and criminalise these practices and have issued statements related to organ commercialism. In contrast, limited attention has been paid to illicit and unethical activities associated with the procurement and clinical use of tissues. In India, The Transplantation of Human Organs (Amendment) Act, 2011, has taken multiple measures to combat organ and tissue commerce and as a result the number of such instances seems to be on the decline. However, the fight against unethical organ procurement through the internet and the social media is challenging and requires the cooperation of global bodies. Keywords: Organ trade, Declaration of Istanbul, tissue commerce, organ transplants, transplant tourism.
Topics: Humans; International Cooperation; Medical Tourism; Organ Trafficking; Organ Transplantation; Tissue and Organ Procurement; Tourism
PubMed: 34730094
DOI: 10.20529/IJME.2021.056