ABSTRACT
Islet transplantation is today an accepted modality for treating selected patients with frequent hypoglycemic events or severe glycemic lability. Despite tremendous progress in islet isolation, culture, and preservation, clinical use is still restricted to a limited subset, and lifelong immunosuppression is required. Issues surrounding limited islet revascularization and immune destruction remain. One of the major challenges is to prevent alloreactivity and recurrence of autoimmunity against ß-cells. These two hurdles can be effectively reduced by immunosuppressive therapy combining induction and maintenance treatments. The introduction of highly potent and selective biologic agents has significantly reduced the frequency of acute rejection and has prolonged graft survival, while minimizing the complications of this therapeutic scheme. This review will address the most important biological agents used in islet transplantation. We provide a historical perspective of their introduction into clinical practice and their role in current clinical protocols, aiming at improved engraftment efficiency, increased long-term survival, and better overall results of clinical islet transplantation.
Subject(s)
Biological Factors/pharmacology , Islets of Langerhans Transplantation , Animals , Biological Factors/history , Biological Factors/therapeutic use , History, 20th Century , Humans , Inflammation/drug therapyABSTRACT
Tudor Griffith's untimely death cut short a research career focused on the mechanisms regulating vascular tone and blood flow. This brief review highlights the contribution that Tudor's work made to 3 main areas: the early days of study toward elucidating the identity of the endothelium-derived relaxing factor (or nitric oxide), the use of computational modeling to unravel the mechanisms underlying the rhythmical arterial contractions known as vasomotion, and the role played by gap junctions in the vasodilatation attributed to endothelium-derived hyperpolarization. Tudor's pioneering application of the connexin mimetic peptides as selective gap junction antagonists has contributed substantially to the current state of knowledge on the role of cell coupling in arterial function. Together, these studies have reemphasized the importance of electromechanical coupling by which changes in membrane potential can rapidly control vessel diameter and blood flow.
Subject(s)
Biological Factors/metabolism , Gap Junctions/metabolism , Vasodilation/physiology , Animals , Biological Factors/history , Connexins/metabolism , History, 20th Century , History, 21st Century , Humans , Membrane Potentials/physiology , Models, Biological , Nitric Oxide/metabolism , Regional Blood Flow/physiologyABSTRACT
The introduction of biological agents has been a major turning-point in the treatment of rheumatic diseases, particularly in rheumatoid arthritis. This review describes the principle milestones that have led, through the knowledge of the structure and functions of nucleic acids, to the development of production techniques of the three major families of biological agents: proteins, monoclonal antibodies and fusion proteins. A brief history has also been traced of the cytokines most involved in the pathogenesis of inflammatory rheumatic diseases (IL-1 and TNF) and the steps which have led to the use of the main biological drugs in rheumatology: anakinra, infliximab, adalimumab, etanercept and rituximab.
Subject(s)
Antirheumatic Agents/history , Biological Factors/history , Rheumatic Diseases/history , Rheumatology/history , Antibodies, Monoclonal/history , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Biological Factors/therapeutic use , Cytokines/antagonists & inhibitors , Cytokines/physiology , DNA/history , DNA, Recombinant/history , Genetic Code , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Molecular Targeted Therapy/history , Nobel Prize , Rheumatic Diseases/drug therapyABSTRACT
David John Faulkner, one of the pioneers of marine natural products chemistry and the 2003 recipient of the ASP Research Achievement Award, passed away on November 23, 2002. John was very pleased to learn that he'd been named as the award recipient and was intending to present the ASP Research Achievement Award Address at the annual meeting in July 2003, Chapel Hill, North Carolina. John's untimely death left an unprecedented event in the history of the ASP-a posthumous Research Achievement Award to a deserving individual and an untimely loss for us all. We are bereft of a colleague, a friend, and a mentor, and the opportunity to hear John's words on the occasion of his own award. In tribute to John, we have assembled a retrospective of John's work that is not meant to be a comprehensive review (this would take considerably more space) but a selection of highlights and personal vignettes from some of those that trained in marine natural products under his mentorship. This paper is a written account of the symposium presented by the authors at the ASP Annual Meeting in Chapel Hill, North Carolina, on July 16, 2003.
Subject(s)
Awards and Prizes , Biological Factors/history , Marine Biology/history , History, 20th Century , History, 21st Century , Humans , Societies, Scientific , United StatesABSTRACT
All of us who have worked with taxol in the laboratory and the clinic, and the many patients all over the world who have benefited from the drug, owe a great debt of gratitude to Monroe Wall, Mansukh Wani, and their colleagues for the initial isolation and characterization of this compound.
Subject(s)
Antineoplastic Agents, Phytogenic/history , Biological Factors/history , Paclitaxel/history , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Biological Factors/chemistry , Biological Factors/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , History, 20th Century , Humans , Microtubules/chemistry , Paclitaxel/chemistry , Paclitaxel/pharmacology , Taxus/chemistry , United StatesSubject(s)
Antineoplastic Agents/isolation & purification , Biological Factors , National Institutes of Health (U.S.) , Animals , Anti-HIV Agents/isolation & purification , Antineoplastic Agents/history , Antineoplastic Agents/therapeutic use , Biological Factors/history , Biological Factors/isolation & purification , Cooperative Behavior , Drug Design , Drug Evaluation/economics , Drug Evaluation/methods , Drug Evaluation, Preclinical/economics , Drug Evaluation, Preclinical/methods , History, 20th Century , Humans , International Cooperation , National Institutes of Health (U.S.)/history , Neoplasms/drug therapy , Plants, Medicinal/chemistry , United StatesSubject(s)
Animals , History, 20th Century , Humans , Antineoplastic Agents/isolation & purification , Biological Factors , National Institutes of Health (U.S.) , Anti-HIV Agents , Antineoplastic Agents/history , Antineoplastic Agents/therapeutic use , Drug Evaluation/economics , Drug Evaluation/methods , Drug Evaluation, Preclinical/economics , Drug Evaluation, Preclinical/methods , Cooperative Behavior , Drug Design , Biological Factors/history , Biological Factors/isolation & purification , International Cooperation , National Institutes of Health (U.S.) , Neoplasms , Plants, Medicinal , United StatesSubject(s)
Alkaloids , Biological Factors/history , Chemistry/history , Plants, Medicinal/chemistry , Tropanes , Acetates/chemistry , Alkaloids/chemical synthesis , Alkaloids/chemistry , Alkaloids/history , Atropine/chemistry , Atropine Derivatives/chemistry , Catalysis , Cobamides/chemistry , Cobamides/metabolism , Cytochrome P-450 Enzyme System/chemistry , Cytochrome P-450 Enzyme System/metabolism , Esters/chemical synthesis , Esters/chemistry , History, 19th Century , History, 20th Century , Models, Molecular , Molecular Structure , Oxidation-Reduction , Pyrrolidines/chemistry , Scopolamine/biosynthesis , Stereoisomerism , Structure-Activity Relationship , Tropanes/chemical synthesis , Tropanes/chemistry , Tropanes/historyABSTRACT
Secondary metabolites, including antibiotics, are produced in nature and serve survival functions for the organisms producing them. The antibiotics are a heterogeneous group, the functions of some being related to and others being unrelated to their antimicrobial activities. Secondary metabolites serve: (i) as competitive weapons used against other bacteria, fungi, amoebae, plants, insects, and large animals; (ii) as metal transporting agents; (iii) as agents of symbiosis between microbes and plants, nematodes, insects, and higher animals; (iv) as sexual hormones; and (v) as differentiation effectors. Although antibiotics are not obligatory for sporulation, some secondary metabolites (including antibiotics) stimulate spore formation and inhibit or stimulate germination. Formation of secondary metabolites and spores are regulated by similar factors. This similarity could insure secondary metabolite production during sporulation. Thus the secondary metabolite can: (i) slow down germination of spores until a less competitive environment and more favorable conditions for growth exist; (ii) protect the dormant or initiated spore from consumption by amoebae; or (iii) cleanse the immediate environment of competing microorganisms during germination.
Subject(s)
Anti-Bacterial Agents , Antibiosis , Biological Factors/physiology , Animals , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/history , Anti-Bacterial Agents/pharmacology , Biological Factors/history , Cell Differentiation , Gonadal Steroid Hormones/history , Gonadal Steroid Hormones/physiology , History, 17th Century , History, 19th Century , History, 20th Century , History, Ancient , History, Medieval , Humans , Industrial Microbiology/history , Metals/metabolism , Siderophores , Spores/metabolism , SymbiosisSubject(s)
Biological Factors , Environment , Political Systems , Population Groups , Public Health , Public Opinion , Biological Factors/history , Biological Factors/physiology , Health Care Reform/economics , Health Care Reform/history , Health Care Reform/legislation & jurisprudence , History, 19th Century , History, 20th Century , Human Characteristics , Humans , Hygiene/economics , Hygiene/education , Hygiene/history , Hygiene/legislation & jurisprudence , Political Systems/history , Politics , Population Groups/education , Population Groups/ethnology , Population Groups/history , Population Groups/legislation & jurisprudence , Population Groups/psychology , Public Health/economics , Public Health/education , Public Health/history , Public Health/legislation & jurisprudence , Public Policy , Social Environment , Spain/ethnologyABSTRACT
El orden médico y el concepto salud-enfermedad. La enfermedad desde la antiguedad hasta el Renacimiento. Las ciencias y la Filosofía. Concepción histórico-social de la enfermedad. Concepción biológica o biologista. La construcción social del criterio de normal y su circulación discursiva.El proceso salud-enfermedad